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Jiang L, Zhu T, Song W, Zhai Y, Tang Y, Ruan F, Xu Z, Li L, Fu X, Liu D, Chen A, Wu Q. Assessment of six insulin resistance surrogate indexes for predicting stroke incidence in Chinese middle-aged and elderly populations with abnormal glucose metabolism: a nationwide prospective cohort study. Cardiovasc Diabetol 2025; 24:56. [PMID: 39915878 PMCID: PMC11804005 DOI: 10.1186/s12933-025-02618-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 01/27/2025] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND Estimate glucose disposal rate (eGDR), Chinese visceral adiposity index (CVAI), triglyceride-glucose (TyG), TyG-body mass index (TyG-BMI), metabolic score for insulin resistance (METS-IR), and atherogenic index of plasma (AIP) are considered surrogate indexes of insulin resistance (IR). There is a lack of studies comparing the predictive values of different IR surrogate indexes for stroke risk among individuals with abnormal glucose metabolism. This study aimed to investigate the relationships between six IR surrogate indexes and stroke risk in individuals with abnormal glucose metabolism, evaluate their predictive abilities for stroke risk. METHODS Data from the China Health and Retirement Longitudinal Study (CHARLS) were analysed in this study. Multivariate logistic regression models were applied to analyse the relationships of IR surrogate indexes with stroke risk. The dose-response relationships between IR surrogate indexes and stroke risk were explored using restricted cubic splines. The areas under the curve (AUCs) of IR surrogate indexes were calculated by receiver operating characteristic (ROC) analysis. RESULTS After adjusting for potential confounders, we observed that each standard deviation (SD) increase in eGDR was associated with a reduced risk of stroke, with an adjusted odds ratio (OR) of 0.746 [95% confidence interval (CI): 0.661-0.842]. In contrast, each SD increase in CVAI, TyG, TyG-BMI, METS-IR, and AIP were associated with an increased risk of stroke, with adjusted ORs (95% CIs) of 1.232 (1.106-1.373), 1.246 (1.050-1.479), 1.186 (1.022-1.376), 1.222 (1.069-1.396), and 1.193 (1.050-1.355), respectively. Dose-response analyses showed that eGDR, CVAI, TyG-BMI and METS-IR were linearly associated with stroke risk (Pnonlinear ≥ 0.05), whereas TyG and AIP were nonlinearly associated with stroke risk (Pnonlinear < 0.05). According to ROC analysis, The AUC of eGDR for predicting stroke risk in the overall population with abnormal glucose metabolism (AUC: 0.612, 95% CI: 0.584-0.640) was significantly higher than that of other indexes. CONCLUSION The six IR surrogate indexes were closely associated with high risk of stroke in individuals with abnormal glucose metabolism. The eGDR showed promising potential in predicting stroke risk in Chinese middle-aged and elderly populations with abnormal glucose metabolism.
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Affiliation(s)
- Luqing Jiang
- Department of Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Tengxiao Zhu
- Department of Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Wenjing Song
- Department of Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Ying Zhai
- Department of Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Yu Tang
- Department of Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Fengxia Ruan
- Department of Laboratory, The Second People's Hospital of Wuhu, Wuhu, Anhui, China
| | - Zichen Xu
- Department of Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Lei Li
- Department of Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Xia Fu
- Department of Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Daoqin Liu
- Department of Nephrology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Aidong Chen
- The Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Qiwen Wu
- Department of Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.
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2
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Cicuéndez B, Mora A, López JA, Curtabbi A, Pérez-García J, Porteiro B, Jimenez-Blasco D, Latorre-Muro P, Vo P, Jerome M, Gómez-Santos B, Romero-Becerra R, Leiva M, Rodríguez E, León M, Leiva-Vega L, Gómez-Lado N, Torres JL, Hernández-Cosido L, Aguiar P, Marcos M, Jastroch M, Daiber A, Aspichueta P, Bolaños JP, Spinelli JB, Puigserver P, Enriquez JA, Vázquez J, Folgueira C, Sabio G. Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis. Nat Commun 2025; 16:229. [PMID: 39805849 PMCID: PMC11730624 DOI: 10.1038/s41467-024-54353-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Accepted: 11/06/2024] [Indexed: 01/16/2025] Open
Abstract
Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident in human and mouse adipose tissue samples. MCJKO mice, even without UCP1, a fundamental thermogenic protein, exhibit elevated BAT thermogenesis. Electron microscopy unveils changes in mitochondrial morphology resembling BAT activation. Proteomic analysis confirms these findings and suggests involvement of the eIF2α mediated stress response. The pivotal role of eIF2α is scrutinized by in vivo CRISPR deletion of eIF2α in MCJKO mice, abrogating thermogenesis. These findings uncover the importance of MCJ as a regulator of BAT thermogenesis, presenting it as a promising target for obesity therapy.
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Grants
- K99 DK133502 NIDDK NIH HHS
- R01 DK136640 NIDDK NIH HHS
- This work has been supported by the following projects: PMP21/00057 funded by the Instituto de Salud Carlos III (ISCIII) - European Union (FEDER/FSE) "Una manera de hacer Europa"/ "El FSE invierte en tu futuro"/ Next Generation EU and cofunded by the European Union / Plan de Recuperación, Transformación y Resiliencia (PRTR); PID2022-138525OB-I00 de la Agencia Estatal de Investigación 10.13039/501100011033, financiado por MICIU/AEI/10.13039/501100011033 fondos FEDER and EU, PDC2021-121147-I00 and PID2019-104399RB-I00 funded by MCIN/AEI/10.13039/501100011033 and the European Union “NextGenerationEU”/Plan de Recuperación Transformación y Resiliencia -PRTR; Grant RED2022-134397-T funded by MCIN/AEI/10.13039/501100011033 and, as appropriate, by “ERDF A way of making Europe”, by the “European Union” or by the “European Union NextGenerationEU/PRTR”; Fundación Jesús Serra; EFSD/Lilly Dr Sabio; 2017 Leonardo Grant BBVA Foundation (Investigadores-BBVA-2017); Comunidad de Madrid IMMUNOTHERCAN-CM S2010/BMD-2326 and B2017/BMD-373; Fundación AECC PROYE19047SABI, PGC2018-097019-B-I00 and PT17/0019/0003- ISCIII-SGEFI /ERDF, ProteoRed. PreMed-Exp: PMP21/00057, PMP21/00113 Infraestructura de Medicina de Precisión asociada a la Ciencia y Tecnología IMPACT-2021 Instituto de Salud Carlos III (GS, JLT).. G.S is a Miembro Numerario of the RACVE. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation) and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).
- A.C was supported by the European Union's Horizon 2020 research and 328 innovation program under the Marie Skłodowska-Curie grant agreement n. 713,673.
- J.P-G was supported by the fellowship from” la Caixa” Foundation (ID 100010434), the fellowship code is LCF/BQ/DR24/12080018.
- M.M is supported by Instituto de Salud Carlos III (ISCIII) and the European Union project PI20/00743.
- P.A is supported by MCIU/AEI/FEDER, UE (PID2021-124425OB-I00) and Basque Government, Department of Education (IT1476-22).
- J.P.B is funded by AEI grants PID2019-105699RB-I00, PID2022-138813OB-I00 and PDC2021-121013-I00; HORIZON-MSCA-2021-DN-01grant 101072759; and La Caixa Research Health grant HR23-00793.
- C.F was funded with Sara Borrell (CD19/ 00078), NNF23SA0083952-EASO/Novo Nordisk New Investigator Award in Basic Sciences 2023, EFSD/Lilly Young Investigator Award 2022, Society for Endocrinology/Early Career Grant 2022, FSEEN/ Jóvenes endocrinólogos 2022, EFSD/Novo Nordisk Rising Star 2024, IBSA Foundation Fellowship Endocrinology 2023.
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Affiliation(s)
- Beatriz Cicuéndez
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- Organ Crosstalk in Metabolic Diseases Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain
| | - Alfonso Mora
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- Organ Crosstalk in Metabolic Diseases Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain
| | - Juan Antonio López
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
| | - Andrea Curtabbi
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
| | - Javier Pérez-García
- Organ Crosstalk in Metabolic Diseases Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain
| | - Begoña Porteiro
- Department of Physiology, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
| | - Daniel Jimenez-Blasco
- Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
- Institute of Functional Biology and Genomics, University of Salamanca, CSIC, Salamanca, Spain
- Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, Salamanca, Spain
| | - Pedro Latorre-Muro
- Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA
- Department of Cell Biology, Harvard Medical School, Boston, MA, USA
| | - Paula Vo
- Program in Molecular Medicine, UMass Chan Medical School, Worcester, MA, USA
| | - Madison Jerome
- Program in Molecular Medicine, UMass Chan Medical School, Worcester, MA, USA
| | - Beatriz Gómez-Santos
- Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU. Leioa, Biobizkaia Health Research Institute, Barakaldo, Spain
| | | | - Magdalena Leiva
- Department of Immunology, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Elena Rodríguez
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- Organ Crosstalk in Metabolic Diseases Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain
| | - Marta León
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- Organ Crosstalk in Metabolic Diseases Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain
| | - Luis Leiva-Vega
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- Organ Crosstalk in Metabolic Diseases Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain
| | - Noemi Gómez-Lado
- Molecular Imaging Biomarkers and Theragnosis Lab, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS). University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Molecular Imaging Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
- Nuclear Medicine Service, University Clinical Hospital of Santiago de Compostela (CHUS), Santiago de Compostela, Spain
| | | | - Lourdes Hernández-Cosido
- Bariatric Surgery Unit. Department of General Surgery, University Hospital of Salamanca. Department of Surgery. University of Salamanca, Salamanca, Spain
| | - Pablo Aguiar
- Molecular Imaging Biomarkers and Theragnosis Lab, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS). University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Molecular Imaging Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
- Nuclear Medicine Service, University Clinical Hospital of Santiago de Compostela (CHUS), Santiago de Compostela, Spain
| | - Miguel Marcos
- Department of Internal Medicine, University Hospital of Salamanca-IBSAL, Salamanca, Spain
- Department of Medicine. University of Salamanca, Salamanca, Spain
| | - Martin Jastroch
- Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
| | - Andreas Daiber
- Department of Cardiology 1, University Medical Center Mainz, Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
| | - Patricia Aspichueta
- Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU. Leioa, Biobizkaia Health Research Institute, Barakaldo, Spain
- Centro de Investigación Biomédica en Red sobre enfermedades hepáticas y digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Juan Pedro Bolaños
- Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
- Institute of Functional Biology and Genomics, University of Salamanca, CSIC, Salamanca, Spain
- Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, Salamanca, Spain
| | - Jessica B Spinelli
- Program in Molecular Medicine, UMass Chan Medical School, Worcester, MA, USA
- UMass Chan Medical School Cancer Center, Worcester, MA, USA
| | - Pere Puigserver
- Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA
- Department of Cell Biology, Harvard Medical School, Boston, MA, USA
| | - José Antonio Enriquez
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
| | - Jesús Vázquez
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
| | - Cintia Folgueira
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
- Organ Crosstalk in Metabolic Diseases Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain.
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.
| | - Guadalupe Sabio
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
- Organ Crosstalk in Metabolic Diseases Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain.
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3
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Li D, Chen Y, Zhu X, Yang Y, Li H, Zhao RC. A novel human specific lncRNA MEK6-AS1 regulates adipogenesis and fatty acid biosynthesis by stabilizing MEK6 mRNA. J Biomed Sci 2025; 32:6. [PMID: 39773638 PMCID: PMC11708274 DOI: 10.1186/s12929-024-01098-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 11/09/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Obesity is becoming one of the major non-communicable diseases with increasing incidence and risks that cannot be ignored. However effective and safe clinical treatment strategies still need to be deeply explored. Increased number and volume of adipocytes lead to overweight and obesity. The aim of our work is to identify lncRNAs that have important regulatory in differentiation of human mesenchymal stem cells (MSCs) into adipocytes, and to provide effective targets for clinical prevention and treatment of obesity and related metabolic disorders. METHODS We extracted primary MSCs from human adipose tissue, and conducted expression profile analysis of lncRNAs during adipogenic differentiation of MSCs to screen changed lncRNAs. Characteristics of lncRNA were revealed mainly by RACE and RNA FISH. Loss- and gain-of function experiments in vivo and in vitro were used to analyze effects of lncRNA. Targeted metabolomics was utilized to detect levels of free fatty acids. RNA pull-down, mRNA stability tests, etc. were employed to explore mechanisms of lncRNA. RESULTS Human-specific lncRNA, we named it MEK6-AS1, was the most up-regulated transcript during adipogenic differentiation of MSCs. MEK6-AS1 was highly expressed in adipose tissue samples from individuals with BMI ≥ 25 and positively correlated with adipogenic marker genes in these samples. Knocking down lncRNA inhibited expression of adipogenic differentiation markers and ectopic adipogenesis, reducing contents of various free fatty acids, as well as promoting osteogenic differentiation. Overexpression of lncRNA had the opposite effects to the above processes. We also found that MEK6-AS1 was elevated during hepatic steatosis organoid generation. Mechanistically, MEK6-AS1 worked partially through stabilization of MEK6 mRNA by NAT10. CONCLUSIONS We have identified a human-specific lncRNA (MEK6-AS1) with position information in the genomic database but has not been extensively reported. We demonstrated that MEK6-AS1 as a novel lncRNA involved in adipogenic differentiation and adipogenesis, fatty acid metabolism, and osteogenic differentiation. We found that MEK6-AS1 may exert its effect by enhancing MEK6 mRNA stability through NAT10. Our study may provide insights into implication of lncRNAs in stem cell biology and offer a new potential therapeutic target for the prevention and treatment of obesity and other related disease.
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Affiliation(s)
- Di Li
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
- Center for Excellence in Tissue Engineering, Chinese Academy of Medical Sciences, Beijing, China
- State Key Laboratory of Common Mechanism Research for Major Diseases, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), Beijing, China
| | - Yunhua Chen
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
- Center for Excellence in Tissue Engineering, Chinese Academy of Medical Sciences, Beijing, China
- State Key Laboratory of Common Mechanism Research for Major Diseases, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), Beijing, China
| | - Xingyu Zhu
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
- Center for Excellence in Tissue Engineering, Chinese Academy of Medical Sciences, Beijing, China
- State Key Laboratory of Common Mechanism Research for Major Diseases, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), Beijing, China
| | - Yanlei Yang
- Clinical Biobank, Department Medical Research Central, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongling Li
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
- Center for Excellence in Tissue Engineering, Chinese Academy of Medical Sciences, Beijing, China.
- State Key Laboratory of Common Mechanism Research for Major Diseases, Chinese Academy of Medical Sciences, Beijing, China.
- Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), Beijing, China.
| | - Robert Chunhua Zhao
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
- Center for Excellence in Tissue Engineering, Chinese Academy of Medical Sciences, Beijing, China.
- State Key Laboratory of Common Mechanism Research for Major Diseases, Chinese Academy of Medical Sciences, Beijing, China.
- Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), Beijing, China.
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4
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Dhritlahre RK, Thakur N, Goel A, Patial V, Padwad Y, Saneja A. Self-Nanoemulsifying Formulation Improves Oral Bioavailability and Insulin Sensitizing Potency of Formononetin-Vitamin E Conjugate in Type 2 Diabetic Mice. Mol Pharm 2025; 22:255-269. [PMID: 39699518 DOI: 10.1021/acs.molpharmaceut.4c00886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2024]
Abstract
The escalating incidence of obesity, diabetes, and insulin resistance has become a significant global health concern. In this study, we have developed a self-nanoemulsifying delivery system (SNEDS) of formononetin-vitamin E conjugate (VESylated-FMN) for improving its oral bioavailability and improving insulin sensitivity and glycemic control. The developed SNEDS were characterized using dynamic light scattering and transmission electron microscopy. Thereafter, the loading capacity, in vitro release, thermodynamic, and gastrointestinal stability of the developed formulation were evaluated. The safety and oral bioavailability of VESylated-FMN-SNEDS were assessed in Sprague-Dawley rats, whereas insulin-sensitizing potency was assessed in high-fat diet-induced type 2 diabetic mice. The VESylated-FMN-SNEDS quickly emulsified on dilution (droplet size ∼79.17 nm) and showed remarkable thermodynamic and gastrointestinal stability. The developed formulation demonstrated enhanced oral bioavailability (∼1.3-fold higher AUC0-t) of VESylated-FMN without liver and kidney injury. Consequently, VESylated-FMN-SNEDS significantly improves insulin sensitivity and glycemic control in HFD-fed mice compared to VESylated-FMN by upregulating the transcript level of insulin-sensitizing genes. Therefore, the SNEDS formulation could be an effective strategy to augment the oral bioavailability and insulin-sensitizing potency of VESylated-FMN.
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Affiliation(s)
- Rakesh Kumar Dhritlahre
- Formulation Laboratory, Dietetics & Nutrition Technology Division, CSIR - Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India
| | - Navneet Thakur
- Formulation Laboratory, Dietetics & Nutrition Technology Division, CSIR - Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
| | - Abhishek Goel
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India
- Pharmacology and Toxicology Laboratory, Dietetics & Nutrition Technology Division, CSIR - Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
| | - Vikram Patial
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India
- Pharmacology and Toxicology Laboratory, Dietetics & Nutrition Technology Division, CSIR - Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
| | - Yogendra Padwad
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India
- Pharmacology and Toxicology Laboratory, Dietetics & Nutrition Technology Division, CSIR - Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
| | - Ankit Saneja
- Formulation Laboratory, Dietetics & Nutrition Technology Division, CSIR - Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India
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Kokkorakis M, Chakhtoura M, Rhayem C, Al Rifai J, Ghezzawi M, Valenzuela-Vallejo L, Mantzoros CS. Emerging pharmacotherapies for obesity: A systematic review. Pharmacol Rev 2025; 77:100002. [PMID: 39952695 DOI: 10.1124/pharmrev.123.001045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 09/03/2024] [Accepted: 09/04/2024] [Indexed: 09/22/2024] Open
Abstract
The history of antiobesity pharmacotherapies is marked by disappointments, often entangled with societal pressure promoting weight loss and the prevailing conviction that excess body weight signifies a lack of willpower. However, categories of emerging pharmacotherapies generate hope to reduce obesity rates. This systematic review of phase 2 and phase 3 trials in adults with overweight/obesity investigates the effect of novel weight loss pharmacotherapies, compared to placebo/control or US Food and Drug Administration-approved weight loss medication, through searching Medline, Embase, and ClinicalTrials.gov (2012-2024). We identified 53 phase 3 and phase 2 trials, with 36 emerging antiobesity drugs or combinations thereof and 4 withdrawn or terminated trials. Oral semaglutide 50 mg is the only medication that has completed a phase 3 trial. There are 14 ongoing phase 3 trials on glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) (ecnoglutide, orforglipron, and TG103), GLP-1 RA/amylin agonist (CagriSema), GLP-1/glucagon RAs (mazdutide and survodutide), GLP-1/glucose-dependent insulinotropic polypeptide and glucagon RA (retatrutide), dapagliflozin, and the combination sibutramine/topiramate. Completed phase 2 trials on incretin-based therapies showed a mean percent weight loss of 7.4% to 24.2%. Almost half of the drugs undergoing phase 2 trials are incretin analogs. The obesity drug pipeline is expanding rapidly, with the most promising results reported with incretin analogs. Data on mortality and obesity-related complications, such as cardio-renal-metabolic events, are needed. Moreover, long-term follow-up data on the safety and efficacy of weight maintenance with novel obesity pharmacotherapies, along with studies focused on underrepresented populations, cost-effectiveness assessments, and drug availability, are needed to bridge the care gap for patients with obesity. SIGNIFICANCE STATEMENT: Obesity is the epidemic of the 21st century. Except for the newer injectable medications, drugs with suboptimal efficacy have been available in the clinician's armamentarium for weight management. However, emerging alternatives of novel agents and combinations populate the current obesity therapeutic pipeline. This systematic review identifies the state and mechanism of action of emerging pharmacotherapies undergoing or having completed phase 2 and phase 3 clinical trials. The information provided herein furthers the understanding of obesity management, implying direct clinical implications and stimulating research initiatives.
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Affiliation(s)
- Michail Kokkorakis
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Marlene Chakhtoura
- Division of Endocrinology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
| | - Caline Rhayem
- Division of Endocrinology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Jana Al Rifai
- Division of Endocrinology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Malak Ghezzawi
- Division of Endocrinology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Laura Valenzuela-Vallejo
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Christos S Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; VA Boston Healthcare System, Harvard Medical School, Boston, Massachusetts.
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6
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Danpanichkul P, Suparan K, Kaeosri C, Jatupornpakdee P, Attia AM, Suenghataiphorn T, Thongpiya J, Sukphutanan B, Huang DQ, Noureddin M, Singal AG, Wijarnpreecha K, Yang JD. Global Trend of MASH-associated Liver Cancer: A Systematic Analysis From the Global Burden of Disease 2021. Clin Gastroenterol Hepatol 2024:S1542-3565(24)01079-6. [PMID: 39694213 DOI: 10.1016/j.cgh.2024.10.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 10/09/2024] [Accepted: 10/10/2024] [Indexed: 12/20/2024]
Abstract
BACKGROUND & AIMS Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are the leading causes of liver disease and are emerging as the main risk factors for primary liver cancer (PLC). However, updated global data on MASH remain scarce. METHODS This study analyzed data from the Global Burden of Disease study between 2000 and 2021 to assess the age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex. RESULTS There were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC globally. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period. Among different etiologies, only MASH-associated PLC had increased mortality rates (annual percent change [APC], +0.46; 95% confidence interval [CI], 0.33%-0.59%). Africa and low sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC. DALYs increased in females (APC, 0.24%; 95% CI, 0.06%-0.42%), whereas they remained stable in males. Americas experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%; 95% CI, 2.02%-2.16%), age-standardized death rate (APC, 1.96%; 95% CI, 1.69%-2.23%), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63%-2.30%) from MASH-associated PLC. CONCLUSIONS Over the past 2 decades, the burden of MASH-associated PLC has risen, though there are sociodemographic and geographic disparities. This necessitates urgent strategies across the globe to mitigate the epidemic of MASH-associated PLC as well as its metabolic drivers.
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Affiliation(s)
- Pojsakorn Danpanichkul
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas
| | - Kanokphong Suparan
- Immunology Unit, Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | | | - Abdelrahman M Attia
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | | | - Jerapas Thongpiya
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas
| | | | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Mazen Noureddin
- Houston Research Institute, Houston Methodist Hospital, Houston, Texas
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona; Department of Internal Medicine, Banner University Medical Center, Phoenix, Arizona; BIO5 Institute, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona.
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
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7
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Danpanichkul P, Suparan K, Tothanarungroj P, Dejvajara D, Rakwong K, Pang Y, Barba R, Thongpiya J, Fallon MB, Harnois D, Lui RN, Wallace MB, Yang JD, Roberts LR, Wijarnpreecha K. Epidemiology of gastrointestinal cancers: a systematic analysis from the Global Burden of Disease Study 2021. Gut 2024; 74:26-34. [PMID: 39242191 DOI: 10.1136/gutjnl-2024-333227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 08/21/2024] [Indexed: 09/09/2024]
Abstract
BACKGROUND Gastrointestinal cancers comprise nearly one-third of global mortality from cancer, yet the comprehensive global burden of these cancers remains uninvestigated. OBJECTIVE We aimed to assess the global, regional and national burden of gastrointestinal cancers. DESIGNS Data on oesophagus, gastric, colorectal, liver, pancreas and biliary tract cancers were extracted from the Global Burden of Disease 2021 database. Age-standardised incidence rate (ASIR) and age-standardised death rate (ASDR) were calculated by sex, region and Sociodemographic Index (SDI). RESULTS In 2021, there were 5.26 million incidences and 3.70 million deaths from gastrointestinal cancer. The greatest burden is from colorectal, followed by gastric, oesophageal, pancreatic, liver and biliary tract cancer. We noted geographical and socioeconomic differences in ASIR and ASDR across all types of cancers. From 2000 to 2021, ASIR increased for colorectal cancer (annual percent change (APC): 0.10%, 95% CI 0.05% to 0.14%), pancreatic cancer (APC: 0.27%, 95% CI 0.14% to 0.41%), and liver cancer from metabolic dysfunction-associated steatotic liver disease (APC: 0.62%, 95% CI 0.58% to 0.67%) and alcohol-related liver disease (APC: 0.26%, 95% CI 0.22% to 0.30%). ASDR increased for pancreatic cancer (APC: 0.18%, 95% CI 0.02% to 0.34%). Higher SDI countries had higher incidence rates for most types of gastrointestinal cancer. CONCLUSIONS Although the ASIR of oesophageal, gastric and biliary tract cancer has decreased, the ASIR still increased in colorectal, pancreatic and liver cancer from steatotic liver disease. Public policies are important for controlling gastrointestinal cancers-most importantly, reducing alcohol consumption, hepatitis B immunisation and tackling the burden of metabolic diseases.
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Affiliation(s)
- Pojsakorn Danpanichkul
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | | | | | | | | | - Yanfang Pang
- Department of Microbiology, Chiang Mai University, Chiang Mai, Thailand
- Affiliated Hospital of Youjiang Medical University of Nationalities, Baise, Guangxi, People's Republic of China
- National Immunological Laboratory for Traditional Chinese Medicine, Baise, Guangxi, People's Republic of China
- Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi, Guangxi, Guangxi, People's Republic of China
| | - Romelia Barba
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Jerapas Thongpiya
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Michael B Fallon
- Division of Gastroenterology and Hepatology, Department of Medicine, The University of Arizona College of Medicine Phoenix, Phoenix, Arizona, USA
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Banner - University Medical Center Phoenix, Phoenix, Arizona, USA
| | - Denise Harnois
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Rashid N Lui
- Institute of Digestive Disease, Chinese University of Hong Kong, New Territories, Hong Kong, People's Republic of China
| | - Michael B Wallace
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Department of Medicine, The University of Arizona College of Medicine Phoenix, Phoenix, Arizona, USA
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Banner - University Medical Center Phoenix, Phoenix, Arizona, USA
- Mayo Clinic Florida, Jacksonville, Florida, USA
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8
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Naanai H, Vartanian LR. Impact of weight and health-behavior information on evaluations of girls' health. J Behav Med 2024:10.1007/s10865-024-00535-w. [PMID: 39633085 DOI: 10.1007/s10865-024-00535-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 11/07/2024] [Indexed: 12/07/2024]
Abstract
The dominant public health narrative equates excess weight with poor health, and previous research has demonstrated that people judge adults with higher body weights as being in poor health, even when they engage in healthy lifestyles. The present study investigated whether the same pattern of beliefs holds for perceptions of children's health. Participants (n = 445) viewed the health profile of a female child that varied in terms of weight status (normal weight, obese), health behaviors (good, poor), and age (younger, older), and then rated the child's overall health and indicated their agreement with suggested behavior recommendations. For older children, targets with obesity were perceived as less healthy and were recommended to engage in more healthy and weight control behaviors than were the targets with normal weight. Health behaviors did influence perceptions of health and behavioral recommendations, but much less so for the target with obesity than for the target with normal weight. For younger children, participants placed a greater emphasis on health behaviors than on weight in their perceptions of the target's health and healthy behavior recommendations, but the target's weight did play a greater role in weight-control behavior recommendations. Overall, perceptions of older children reflect the mainstream weight-centric health beliefs that are perpetuated in public health messaging, whereas perceptions of younger children seem to be more aligned with the scientific evidence supporting the importance of health behaviors to overall health. Public health messaging, particularly messaging targeting parents, should be reframed to focus on the importance of engagement with health behaviors without reference to weight.
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Affiliation(s)
- Habiba Naanai
- School of Psychology, UNSW Sydney, Sydney, NSW, 2052, Australia
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9
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Lam CCB, Mina T, Xie W, Low YD, Yew YW, Wang X, Riboli E, Elliott P, Lee J, Ngeow J, Lee ES, Loh M, Chambers JC. The relationships between sleep and adiposity amongst multi-ethnic Asian populations: a cross-sectional analysis of the Health for Life in Singapore (HELIOS) study. Int J Obes (Lond) 2024:10.1038/s41366-024-01666-5. [PMID: 39562689 DOI: 10.1038/s41366-024-01666-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 10/23/2024] [Accepted: 10/28/2024] [Indexed: 11/21/2024]
Abstract
BACKGROUND Short sleep duration and poor sleep quality have been associated with obesity. Asian populations report shorter sleep duration compared to other groups. We therefore aimed to explore the relationships between sleep duration, sleep quality, dozing, daytime napping, snoring, insomnia and adiposity in a multi-ethnic Asian population, and investigate the potential contribution of disturbed sleep to the risk of obesity amongst Asian populations. METHODS We studied 8876 participants of the HELIOS study, a multi-ethnic population-based cohort comprising Chinese, Malay, and Indian Asian men and women living in Singapore. Sleep traits and psychological symptoms were assessed using validated tools which included the Pittsburg Sleep Quality Index, Generalised Anxiety Disorder-7, and Patient Health Questionnaire-9. We employed multivariable regression models to examine the associations between sleep and adiposity, while also conducting sub-group and sensitivity analyses to strengthen the reliability of our results. RESULTS The 8876 participants were 69.3% Chinese, 12.5% Malays, and 18.2% Indians, with mean age: 51.7 ± 11.8 years (standard deviation). Malays had the shortest sleep duration, while Chinese had the best sleep quality. Short sleep duration, poor sleep quality, and snoring were associated with higher BMI and waist circumference, independent of age, sex, ethnicity, and various confounding factors (education, household income, current smoking, regular alcohol drinking status, presence of diabetes and hypertension, and markers for anxiety and depression; P < 0.005). The estimated population attributable fraction for short sleep and snoring as contributors to obesity were 6.6% (95% CI: 2.5-10.6%) and 18.6% (95% CI: 17.0-20.2%), respectively. CONCLUSION Sleep duration, sleep quality, and snoring are associated with adiposity in a multi-ethnic Asian population of Chinese, Malays, and Indians. Our findings suggest that a substantial portion of obesity in Asian populations could be averted through public health interventions aimed at improving sleep duration and quality.
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Affiliation(s)
- Chih Chiang Benjamin Lam
- Khoo Teck Puat Hospital, Singapore, Singapore.
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
| | - Theresia Mina
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Wubin Xie
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Yanwen Dorrain Low
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Yik Weng Yew
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- National Skin Centre, Singapore, Singapore
| | - Xiaoyan Wang
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK
| | - Paul Elliott
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK
| | - Jimmy Lee
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- North Region, Institute of Mental Health, Singapore, Singapore
| | - Joanne Ngeow
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- Division of Medical Oncology, National Cancer Centre, Singapore, Singapore
| | - Eng Sing Lee
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- Clinical Research Unit, National Healthcare Group Polyclinics, Singapore, Singapore
| | - Marie Loh
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- National Skin Centre, Singapore, Singapore
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK
| | - John C Chambers
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK
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10
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de Oliveira Vogado C, Ferreira MA, Nakano EY, Azevedo S, Magalhães KG, Fernandes Arruda S, Botelho PB. Interaction between green tea and metformin and its effects on oxidative stress and inflammation in overweight women: a randomised clinical trial. Br J Nutr 2024:1-9. [PMID: 39494829 DOI: 10.1017/s0007114524002356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2024]
Abstract
This study evaluated the effect of green tea extract and metformin and its interaction on markers of oxidative stress and inflammation in overweight women with insulin resistance. After screening, 120 women were randomly allocated in 4 groups: Placebo (PC): 1g of microcrystalline cellulose/day; Green tea (GT): 1 g (558 mg polyphenols) of standardized dry extract of green tea/day and 1 g of placebo/day; Metformin (MF): 1 g of metformin/day and 1 g of placebo/day; Green Tea and Metformin (GTMF): 1 g (558 mg polyphenols) and 1 g of metformin/day. All groups were followed-up for 12 weeks with assessment of oxidative damage to lipids and proteins, specific activity of antioxidant enzymes and inflammatory cytokine serum levels. The association of green tea with metformin significantly reduced IL-6 (GTMF: -29.7((-62.6)-20.2))(p = 0.004). Green tea and metformin isolated reduced TNF-α (GT: -12.1((-18.0)-(-3.5)); MF: -24.5((-38.60)-(-4.4)) compared to placebo (PB: 13.8 (1.2-29.2))(P < 0.001). Also, isolated metformin reduced TGF-β (MF: -25.1((-64.4)-0.04)) in comparison to placebo (PB: 6.3((-1.0)-16.3))(p = 0.038). However, when combined, their effects were nullified either for TNF-α (GTMF: 6.0((-5.7)-23.9) and for TGF-β (GTMF: -1.8((-32.1)-8.5). This study showed that there is a drug-nutrient interaction between green tea and metformin that is dependent on the cytokine analyzed.
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Affiliation(s)
| | - Monalisa Alves Ferreira
- Laboratory of Research in Clinical Nutrition and Sports, Nutrition Faculty, Federal University of Goias, Goiania, Goias, Brazil
| | | | - Sabrina Azevedo
- Laboratory of Immunology and Inflammation, Department of Cellular Biology, University of Brasília, Brasília, Brazil
| | - Kelly Grace Magalhães
- Laboratory of Immunology and Inflammation, Department of Cellular Biology, University of Brasília, Brasília, Brazil
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11
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Halasz M, Łuczaj W, Jarocka-Karpowicz I, Stasiewicz A, Soldo AM, Soldo I, Pajtak A, Senčar M, Grgić T, Kolak T, Žarković N, Skrzydlewska E, Jaganjac M. Relationship between systemic biomarker of lipid peroxidation 4-hydroxynonenal and lipidomic profile of morbidly obese patients undergoing bariatric surgery. Free Radic Biol Med 2024; 224:564-573. [PMID: 39278574 DOI: 10.1016/j.freeradbiomed.2024.09.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 08/23/2024] [Accepted: 09/12/2024] [Indexed: 09/18/2024]
Abstract
Obesity is characterized by fat accumulation, impaired metabolism and oxidative stress, frequently associated with lipid peroxidation and generation of bioactive 4-hydroxynonenal (4-HNE). This study aimed to evaluate the impact of bariatric surgery-induced weight loss on lipid peroxidation and associated perturbations in lipid profile. Plasma samples of twenty obese individuals before and 6 months after bariatric surgery were collected in addition to samples of ten healthy controls. HILIC-LC-MS/MS platform was used to characterize phospholipid profile, while lipid peroxidation markers 15-F2t-IsoP, 10-F4t-NeuroP and reactive aldehyde 4-HNE were quantified by RP-LC-MS/MS and GC-MS, respectively. Six months post-surgery lipid peroxidation markers decreased significantly and the BMI of morbidly obese patients decreased by 13 on average. Lipidomics analysis, identified 117 phospholipid species from seven classes, and showed obesity-associated lipidome perturbations, particularly in ether-linked phosphatidylethanolamines (PEo). A total of 45 lipid species were found to be significantly altered with obesity, while 10 lipid species correlated with lipid peroxidation markers. Sample pairwise analyses indicated an interesting link between 4-HNE and the amount of two PEos, PEo (38:2) and PEo (36:2). The results indicate that weight loss-induced improvement of redox homeostasis together with changes in lipid metabolites may serve as markers of metabolic improvement. However, further studies are needed to understand the role of obesity-induced oxidative stress on ether lipid biosynthesis and lipidome perturbations, as well as the impact of bariatric surgery on metabolic improvement.
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Affiliation(s)
- Mirna Halasz
- Laboratory for Oxidative Stress, Division of Molecular Medicine, Ruder Boskovic Institute, 10000, Zagreb, Croatia
| | - Wojciech Łuczaj
- Department of Analytical Chemistry, Medical University of Białystok, 15-222 Białystok, Poland
| | - Iwona Jarocka-Karpowicz
- Department of Analytical Chemistry, Medical University of Białystok, 15-222 Białystok, Poland
| | - Anna Stasiewicz
- Department of Analytical Chemistry, Medical University of Białystok, 15-222 Białystok, Poland
| | - Ana Maria Soldo
- Internal Medicine Clinic, University Hospital "Sveti Duh", Zagreb, Croatia
| | - Ivo Soldo
- Surgery Clinic, University Hospital "Sveti Duh", Zagreb, Croatia
| | - Alen Pajtak
- Department of Abdominal Surgery, General Hospital Varazdin, Varazdin, Croatia
| | - Marin Senčar
- Department of Abdominal Surgery, General Hospital Varazdin, Varazdin, Croatia
| | - Tihomir Grgić
- Surgery Clinic, University Hospital "Sveti Duh", Zagreb, Croatia
| | - Toni Kolak
- Department of Abdominal Surgery, University Hospital Dubrava, Zagreb, Croatia
| | - Neven Žarković
- Laboratory for Oxidative Stress, Division of Molecular Medicine, Ruder Boskovic Institute, 10000, Zagreb, Croatia
| | - Elżbieta Skrzydlewska
- Department of Analytical Chemistry, Medical University of Białystok, 15-222 Białystok, Poland.
| | - Morana Jaganjac
- Laboratory for Oxidative Stress, Division of Molecular Medicine, Ruder Boskovic Institute, 10000, Zagreb, Croatia.
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12
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Chen Y, Jin J, Zhang P, Ye R, Zeng C, Zhang Y, Chen J, Li H, Xiao H, Li Y, Guan H. Clinical Impact of Obesity on Postoperative Outcomes of Patients With Thyroid Cancer Undergoing Thyroidectomy: A 5-Year Retrospective Analysis From the US National Inpatient Sample. Cancer Med 2024; 13:e70335. [PMID: 39417377 PMCID: PMC11483747 DOI: 10.1002/cam4.70335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 02/21/2024] [Accepted: 09/30/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND The clinical impact of obesity on postoperative outcomes of patients undergoing thyroidectomy remains controversial. METHODS Patients aged ≥ 18 years who were diagnosed with thyroid malignancy and underwent thyroidectomy between 2016 and 2020 were included, and divided into two groups: patients with body mass index (BMI) < 30 kg/m2 and those with BMI ≥ 30 kg/m2. Patients in the obese group were then subdivided into four groups: Group 1 (BMI 30.0-34.9 kg/m2), Group 2 (BMI 35.0-39.9 kg/m2), Group 3 (BMI 40.0-44.9 kg/m2), and Group 4 (BMI ≥ 45.0 kg/m2) to evaluate the association between degree of obesity and clinical outcomes. We performed propensity score matching, compared outcome variables between the groups, and conducted adjusted multivariate logistic regression analyses of postoperative outcomes. RESULTS A total of 6778 patients diagnosed with thyroid cancer who underwent thyroidectomy were screened, of whom 1299 (19.2%) patients were obese. Patients in the obese group had higher total hospital charges (p < 0.001) and an increased risk of overall postoperative complications (34.7% vs. 30.5%, p = 0.023). Specifically, patients in the obese group had increased odds of respiratory complication (adjusted odds ratio (aOR) 1.66, 95% confidence interval (CI) [1.26-2.19]), acute renal failure (aOR 1.87, 95% CI [1.13-3.09]), and wound complication (aOR 2.77, 95% CI [1.21-6.37]) than those in the non-obese group. Moreover, trend tests showed that the risks of unfavorable discharge, infection, acute renal failure, and respiratory complication all exhibited an upward trend with increased BMI. CONCLUSION Obesity is associated with an increased risk of postoperative complications in patients with thyroid cancer undergoing thyroidectomy. This finding suggests that obese patients should be treated with more caution during postoperative recovery.
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Affiliation(s)
- Yue Chen
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Jiewen Jin
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Pengyuan Zhang
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Runyi Ye
- Department of Breast SurgeryThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouGuangdongChina
| | - Chuimian Zeng
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
- Zhongshan School of MedicineSun Yat‐sen UniversityGuangzhouChina
| | - Yilin Zhang
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
- Zhongshan School of MedicineSun Yat‐sen UniversityGuangzhouChina
| | - Junxin Chen
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Hai Li
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Haipeng Xiao
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Yanbing Li
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Hongyu Guan
- Department of Endocrinology and Diabetes CenterThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
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Bausek N, Woodard J, Boeder M, Turinske TJ, Stiles A, Lipset M, Meyer NJ. A novel structured, volume-based, weight-loss and health programme combined with respiratory muscle training helps reduce weight and cardiovascular risk in people with obesity. Diabetes Obes Metab 2024; 26:4772-4775. [PMID: 39082073 DOI: 10.1111/dom.15795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 06/28/2024] [Accepted: 06/30/2024] [Indexed: 09/19/2024]
Affiliation(s)
- Nina Bausek
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Jacob Woodard
- Department of Biology and Anthropology, University of Central Florida, Orlando, Florida, USA
| | - MiKinze Boeder
- University of Minnesota Medical School, Duluth, Minnesota, USA
| | - Thomas J Turinske
- Chicago Medical School, Rosalind Franklin University, North Chicago, Illinois, USA
| | | | - Max Lipset
- Health Quotient, St Louis Park, Minnesota, USA
| | - Nicholas J Meyer
- ProportionFit, Twin Cities Orthopedics, Woodbury, Minnesota, USA
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Letukienė A, Hendrixson V, Ginevičienė V. Current knowledge and scientific trends in myokines and exercise research in the context of obesity. Front Med (Lausanne) 2024; 11:1421962. [PMID: 39376657 PMCID: PMC11456489 DOI: 10.3389/fmed.2024.1421962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 09/10/2024] [Indexed: 10/09/2024] Open
Abstract
The relationship between exercise and obesity has attracted increasing attention from researchers worldwide in recent years. The aim of the present study was to analyze the current knowledge and scientific trends of research into myokines and exercise in the context of obesity and provide ideas for future research strategies to prevent obesity. The study conducted a comprehensive bibliometric analysis of 300 scientific publications related to myokines, exercise, and obesity from 2004 to 2024. Applying the VOSviewer tool, the analysis revealed a significant increase over time in the number of publications on these topics, with a total of 1,142 related keywords identified. Key themes identified in the analysis included molecular processes, new organokines, skeletal muscle research, model organism studies, and human studies based on sex and age differences. The study highlighted the growing interest in the molecular mechanisms of obesity and role of myokines. Results showed a substantial increase in publications from 2014 to 2024, with a focus on new organokines (myokines, adipokines) and animal models. The analysis underscored the importance of myokines in modulating metabolic processes and their potential therapeutic implications in managing non-communicable diseases such as obesity. Furthermore, the study revealed the close relationship between exercise, myokine production, and regulation of metabolism, stress response, and inflammation. In conclusion, over the last years, increasing research interest has been focused on the molecular mechanisms of obesity and benefits of exercise, and probably will be focused on a set of myokines released during muscle contraction. A newly identified myokines has emerged as a promising marker for the prevention and control of obesity.
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15
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Wang D, Benito PJ, Rubio-Arias JÁ, Ramos-Campo DJ, Rojo-Tirado MA. Exploring factors of adherence to weight loss interventions in population with overweight/obesity: an umbrella review. Obes Rev 2024; 25:e13783. [PMID: 38807509 DOI: 10.1111/obr.13783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 07/31/2023] [Accepted: 04/28/2024] [Indexed: 05/30/2024]
Abstract
Adherence is key for achieving the optimal benefits from a weight loss intervention. Despite the number of studies on factors that promote adherence, their findings suggest inconsistent and fragmented evidence. The aim of this study was to review the existing factors of adherence to weight loss interventions and to find factors that facilitate the design of effective intervention programs. Six databases were searched for this umbrella review; after the screening process, 21 studies were included. A total of 47 factors were identified in six groups as relevant for adherence: (i) sociodemographic (n = 7), (ii) physical activity (n = 2), (iii) dietary (n = 8), (iv) behavioral (n = 4), (v) pharmacological (n = 3), and (vi) multi-intervention (n = 23). In addition, a map of adherence factors was created. The main findings are that with respect to demographic factors, the development of personalized intervention strategies based on the characteristics of specific populations is encouraged. Moreover, self-monitoring has been shown to be effective in behavioral, dietary, and multi-interventions, while technology has shown potential in dietary, behavioral, and multi-interventions. In addition, multi-interventions are adherence-promoting strategies, although more evidence is required on adherence to pharmacological interventions. Overall, the factor map can be controlled and modified by researchers and practitioners to improve adherence to weight loss interventions.
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Affiliation(s)
- Deng Wang
- LFE Research Group, Department of Health and Human Performance, Faculty of Physical Activity and Sport Science (INEF), Universidad Politécnica de Madrid (UPM), Madrid, Spain
| | - Pedro J Benito
- LFE Research Group, Department of Health and Human Performance, Faculty of Physical Activity and Sport Science (INEF), Universidad Politécnica de Madrid (UPM), Madrid, Spain
| | - Jacobo Á Rubio-Arias
- Health Research Centre, Department of Education, Faculty of Educational Sciences, University of Almería, Almería, Spain
| | - Domingo J Ramos-Campo
- LFE Research Group, Department of Health and Human Performance, Faculty of Physical Activity and Sport Science (INEF), Universidad Politécnica de Madrid (UPM), Madrid, Spain
| | - Miguel A Rojo-Tirado
- LFE Research Group, Department of Health and Human Performance, Faculty of Physical Activity and Sport Science (INEF), Universidad Politécnica de Madrid (UPM), Madrid, Spain
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16
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Luca T, Pezzino S, Puleo S, Castorina S. Lesson on obesity and anatomy of adipose tissue: new models of study in the era of clinical and translational research. J Transl Med 2024; 22:764. [PMID: 39143643 PMCID: PMC11323604 DOI: 10.1186/s12967-024-05547-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Accepted: 07/28/2024] [Indexed: 08/16/2024] Open
Abstract
Obesity is a serious global illness that is frequently associated with metabolic syndrome. Adipocytes are the typical cells of adipose organ, which is composed of at least two different tissues, white and brown adipose tissue. They functionally cooperate, interconverting each other under physiological conditions, but differ in their anatomy, physiology, and endocrine functions. Different cellular models have been proposed to study adipose tissue in vitro. They are also useful for elucidating the mechanisms that are responsible for a pathological condition, such as obesity, and for testing therapeutic strategies. Each cell model has its own characteristics, culture conditions, advantages and disadvantages. The choice of one model rather than another depends on the specific study the researcher is conducting. In recent decades, three-dimensional cultures, such as adipose spheroids, have become very attractive because they more closely resemble the phenotype of freshly isolated cells. The use of such models has developed in parallel with the evolution of translational research, an interdisciplinary branch of the biomedical field, which aims to learn a scientific translational approach to improve human health and longevity. The focus of the present review is on the growing body of data linking the use of new cell models and the spread of translational research. Also, we discuss the possibility, for the future, to employ new three-dimensional adipose tissue cell models to promote the transition from benchside to bedsite and vice versa, allowing translational research to become routine, with the final goal of obtaining clinical benefits in the prevention and treatment of obesity and related disorders.
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Affiliation(s)
- Tonia Luca
- Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Via Santa Sofia, 87, Catania, 95123, Italy.
| | | | - Stefano Puleo
- Mediterranean Foundation "GB Morgagni", Catania, Italy
| | - Sergio Castorina
- Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Via Santa Sofia, 87, Catania, 95123, Italy
- Mediterranean Foundation "GB Morgagni", Catania, Italy
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17
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Zhang J, Huang Y, Li H, Xu P, Liu Q, Sun Y, Zhang Z, Wu T, Tang Q, Jia Q, Xia Y, Xu Y, Jing X, Li J, Mo L, Xie W, Qu A, He J, Li Y. B3galt5 functions as a PXR target gene and regulates obesity and insulin resistance by maintaining intestinal integrity. Nat Commun 2024; 15:5919. [PMID: 39004626 PMCID: PMC11247088 DOI: 10.1038/s41467-024-50198-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 07/03/2024] [Indexed: 07/16/2024] Open
Abstract
Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of β-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.
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Affiliation(s)
- Jinhang Zhang
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Ya Huang
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
- Department of Pharmacy, GuiQian International General Hospital, Guiyang, China
| | - Hong Li
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Pengfei Xu
- Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA
| | - Qinhui Liu
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yang Sun
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan Province, China
| | - Zijing Zhang
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Tong Wu
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Qin Tang
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Qingyi Jia
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yan Xia
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Ying Xu
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xiandan Jing
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Jiahui Li
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Li Mo
- Center of Gerontology and Geriatrics, West China Hospital of Sichuan University, Chengdu, China
| | - Wen Xie
- Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA
| | - Aijuan Qu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China
| | - Jinhan He
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
| | - Yanping Li
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
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18
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Mun SK, Jang CJ, Jo S, Park SH, Sim HB, Ramos SC, Kim H, Choi YJ, Park DH, Park KW, Jeong BG, Kim DH, Kang KY, Kim JJ. Anti-obesity and immunomodulatory effects of oil and fermented extract dried from Tenebrio molitor larvae on aged obese mice. Anim Cells Syst (Seoul) 2024; 28:340-352. [PMID: 39011371 PMCID: PMC11249154 DOI: 10.1080/19768354.2024.2374547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 06/24/2024] [Indexed: 07/17/2024] Open
Abstract
Preventing disease and maintaining the health of the elderly are crucial goals for an aging population, with obesity and immune function restoration being of paramount importance. Obesity, particularly visceral obesity characterized by excessive fat accumulation around the abdominal organs, is linked to chronic conditions such as diabetes, hypertension, cardiovascular diseases, and immune dysfunction. Globally, obesity is considered a disease, prompting significant research interest in its treatment. Therefore, it is essential to explore potential therapeutic and preventive strategies to address obesity and the decline in immune function brought about by aging. Tenebrio molitor larvae (TML), commonly known as 'mealworms,' are rich in unsaturated fatty acids, including oleic and linoleic acids, and essential amino acids, such as isoleucine and tyrosine. In this study, we aimed to investigate the effects of the consumption of TML oil and mealworm fermented extract (MWF-1) on obesity and immunological changes in aged obese mice. Our data showed reduced body fat in 23-week-old C57BL/6 mice fed processed TML products for 6 weeks. Additionally, the characteristically high levels of serum triglycerides decreased by treating with TML oil. The immune responsiveness results confirmed an increase in B cells by treating with MWF-1, while cytokine levels (interferon-gamma, tumor necrosis factor-alpha, interleukin-2, and -6) were restored to levels similar to young mice. These results suggest that TML oil and MWF-1 are promising dietary supplements for addressing obesity and restoring immune function.
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Affiliation(s)
- Seul-Ki Mun
- Department of Biomedical Science, Sunchon National University, Suncheon, Republic of Korea
| | - Chang Joo Jang
- Department of Biomedical Science, Sunchon National University, Suncheon, Republic of Korea
| | - Semi Jo
- Department of Biomedical Science, Sunchon National University, Suncheon, Republic of Korea
| | - Si-Hyoun Park
- Department of Biomedical Science, Sunchon National University, Suncheon, Republic of Korea
| | - Hyun Bo Sim
- Department of Biomedical Science, Sunchon National University, Suncheon, Republic of Korea
| | - Sonny C Ramos
- Department of Biomedical Science, Sunchon National University, Suncheon, Republic of Korea
| | - Hyeongyeong Kim
- Department of Biomedical Science, Sunchon National University, Suncheon, Republic of Korea
| | - Yu-Jeong Choi
- Department of Biomedical Science, Sunchon National University, Suncheon, Republic of Korea
| | - Dae-Han Park
- Department of Biomedical Science, Sunchon National University, Suncheon, Republic of Korea
| | - Kyung-Wuk Park
- R&D team, Suncheon Research Center for Bio Health Care, Suncheon, Republic of Korea
| | - Beom-Gyun Jeong
- R&D team, Suncheon Research Center for Bio Health Care, Suncheon, Republic of Korea
| | - Dae Heon Kim
- Department of Biomedical Science, Sunchon National University, Suncheon, Republic of Korea
- CCRIPO Inc., Daejeon, Republic of Korea
| | - Kyung-Yun Kang
- R&D team, Suncheon Research Center for Bio Health Care, Suncheon, Republic of Korea
| | - Jong-Jin Kim
- Department of Biomedical Science, Sunchon National University, Suncheon, Republic of Korea
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19
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Truong HG, Nagengast AA, DiAngelo JR. The regulation of carnitine palmitoyltransferase 1 ( CPT1) mRNA splicing by nutrient availability in Drosophila fat tissue. Biochem Biophys Rep 2024; 38:101661. [PMID: 38384389 PMCID: PMC10879661 DOI: 10.1016/j.bbrep.2024.101661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 02/03/2024] [Accepted: 02/08/2024] [Indexed: 02/23/2024] Open
Abstract
After a meal, excess nutrients are stored within adipose tissue as triglycerides in lipid droplets. Previous genome-wide RNAi screens in Drosophila cells have identified mRNA splicing factors as being important for lipid droplet formation. Our lab has previously shown that a class of mRNA splicing factors called serine/arginine-rich (SR) proteins, which help to identify intron/exon borders, are important for triglyceride storage in Drosophila fat tissue, partially by regulating the splicing of the gene for carnitine palmitoyltransferase 1 (CPT1), an enzyme important for mitochondrial β-oxidation of fatty acids. The CPT1 gene in Drosophila generates two major isoforms, with transcripts that include exon 6A producing more active enzymes than ones made from transcripts containing exon 6B; however, whether nutrient availability regulates CPT1 splicing in fly fat tissue is not known. During ad libitum feeding, control flies produce more CPT1 transcripts containing exon 6B while fasting for 24 h results in a shift in CPT1 splicing to generate more transcripts containing exon 6A. The SR protein 9G8 is necessary for regulating nutrient responsive CPT1 splicing as decreasing 9G8 levels in fly fat tissue blocks the accumulation of CPT1 transcripts including exon 6A during starvation. Protein kinase A (PKA), a mediator of starvation-induced lipid breakdown, also regulates CPT1 splicing during starvation as transcripts including exon 6A did not accumulate when PKA was inhibited during starvation. Together, these results indicate that CPT1 splicing in adipose tissue responds to changes in nutrient availability contributing to the overall control of lipid homeostasis.
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Affiliation(s)
- Huy G. Truong
- Division of Science, Penn State Berks, Reading, PA, USA
| | - Alexis A. Nagengast
- Departments of Chemistry and Biochemistry, Widener University, Chester, PA, USA
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20
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Mederos-Torres CV, Díaz-Burke Y, Muñoz-Almaguer ML, García-Zapién AG, Uvalle-Navarro RL, González-Sandoval CE. Triglyceride/high-density cholesterol ratio as a predictor of cardiometabolic risk in young population. J Med Life 2024; 17:722-727. [PMID: 39440341 PMCID: PMC11493158 DOI: 10.25122/jml-2024-0117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 06/30/2024] [Indexed: 10/25/2024] Open
Abstract
Cardiovascular disease remains a leading cause of morbidity and mortality worldwide. Understanding and detecting risk factors are crucial for early diagnosis and prevention strategies. Obesity, dyslipidemia, hypertension, and insulin resistance, among others, have been described as modifiable risk factors. Among these, the triglycerides-to-HDL cholesterol (TG/HDL) ratio has been described as a marker of insulin resistance and a predictor of cardiovascular disease. Our objective was to investigate the association between the TG/HDL ratio and various cardiometabolic risk factors. A total of 239 young adults aged 18-24 years were recruited. We assessed anthropometric measurements, lipid profiles, glucose levels, insulin, the HOMA index, and the TG/HDL ratio. Participants were stratified based on their BMI and TG/HDL ratio. Our findings revealed that individuals with an elevated TG/HDL ratio had higher blood pressure, BMI, waist circumference, cholesterol, and triglyceride levels compared to those with a normal ratio. Specifically, the TG/HDL ratio was associated with an odds ratio (OR) of 9.3 for overweight, 27.5 for obesity, and 4.41 for abdominal obesity. Additionally, the HOMA index, which measures insulin resistance, was higher in those with an elevated TG/HDL ratio, with a prevalence of 45.6%. In conclusion, the TG/HDL ratio is a predictive marker of insulin resistance in young individuals and is associated with modifiable risk factors for cardiometabolic disease.
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Affiliation(s)
- Claudia Veronica Mederos-Torres
- Department of Pharmacobiology, University Center for Exact Sciences and Engineering, University of Guadalajara, Guadalajara, Mexico
| | - Yolanda Díaz-Burke
- Department of Pharmacobiology, University Center for Exact Sciences and Engineering, University of Guadalajara, Guadalajara, Mexico
- Academic Body UDG-CA-156 Biomedical Science and Toxicology, University of Guadalajara, Guadalajara, Mexico
| | - María Luisa Muñoz-Almaguer
- Department of Pharmacobiology, University Center for Exact Sciences and Engineering, University of Guadalajara, Guadalajara, Mexico
- Academic Body UDG-CA-156 Biomedical Science and Toxicology, University of Guadalajara, Guadalajara, Mexico
| | | | - Rosario Lizette Uvalle-Navarro
- Department of Pharmacobiology, University Center for Exact Sciences and Engineering, University of Guadalajara, Guadalajara, Mexico
| | - Claudia Elena González-Sandoval
- Department of Pharmacobiology, University Center for Exact Sciences and Engineering, University of Guadalajara, Guadalajara, Mexico
- Academic Body UDG-CA-156 Biomedical Science and Toxicology, University of Guadalajara, Guadalajara, Mexico
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21
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Zeng B, Shen Q, Wang B, Tang X, Jiang J, Zheng Y, Huang H, Zhuo W, Wang W, Gao Y, Li X, Wang S, Li W, Qian G, Qin J, Hou M, Lv H. Spexin ameliorated obesity-related metabolic disorders through promoting white adipose browning mediated by JAK2-STAT3 pathway. Nutr Metab (Lond) 2024; 21:22. [PMID: 38658956 PMCID: PMC11040786 DOI: 10.1186/s12986-024-00790-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 03/13/2024] [Indexed: 04/26/2024] Open
Abstract
BACKGROUND Spexin, a 14 amino acid peptide, has been reported to regulate obesity and its associated complications. However, little is known about the underlying molecular mechanism. Therefore, this study aimed to investigate the effects of spexin on obesity and explore the detailed molecular mechanisms in vivo and in vitro. METHODS Male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity, and mice fed a standard fat diet were used as controls. Then, these mice were treated with SPX or Vehicle by intraperitoneal injection for an additional 12 weeks, respectively. The metabolic profile, fat-browning specific markers and mitochondrial contents were detected. In vitro, 3T3-L1 cells were used to investigate the molecular mechanisms. RESULTS After 12 weeks of treatment, SPX significantly decreased body weight, serum lipid levels, and improved insulin sensitivity in HFD-induced obese mice. Moreover, SPX was found to promote oxygen consumption in HFD mice, and it increased mitochondrial content as well as the expression of brown-specific markers in white adipose tissue (WAT) of HFD mice. These results were consistent with the increase in mitochondrial content and the expression of brown-specific markers in 3T3-L1 mature adipocytes. Of note, the spexin-mediated beneficial pro-browning actions were abolished by the JAK2/STAT3 pathway antagonists in mature 3T3-L1 cells. CONCLUSIONS These data indicate that spexin ameliorates obesity-induced metabolic disorders by improving WAT browning via activation of the JAK2/STAT3 signaling pathway. Therefore, SPX may serve as a new therapeutic candidate for treating obesity.
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Affiliation(s)
- Bihe Zeng
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
- Department of Pediatrics, Affiliated Huai'an Hospital of Xuzhou Medical University, 223002, Huai'an, China
| | - Qin Shen
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Bo Wang
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Xuan Tang
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Jiaqi Jiang
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Yiming Zheng
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Hongbiao Huang
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Wenyu Zhuo
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Wang Wang
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Yang Gao
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Xuan Li
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Shuhui Wang
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Wenjie Li
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Guanghui Qian
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Jie Qin
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China
| | - Miao Hou
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China.
| | - Haitao Lv
- Department of Cardiology, Children's Hospital of Soochow University, 215025, Suzhou, China.
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Bashyal S, Qu S, Karki M. Bariatric Surgery and Its Metabolic Echo Effect on Serum Uric Acid Levels. Cureus 2024; 16:e58103. [PMID: 38616980 PMCID: PMC11013573 DOI: 10.7759/cureus.58103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/12/2024] [Indexed: 04/16/2024] Open
Abstract
Bariatric surgery (BS) has been a significant means of reducing weight in obese individuals. The metabolic changes after bariatric surgery are crucial as they extend its advantages beyond weight loss. As its name implies, "metabolic surgery" also addresses obesity-related metabolic concerns. Bariatric surgery has always been associated with lessened serum uric acid (SUA) levels. In this review, we examined current studies to understand how surgical therapies impact serum uric acid levels. Strongly minded on the extent and timing of changes in the level of serum uric acid after bariatric surgeries. We conducted a comprehensive search for relevant current studies in PubMed, Google Scholar, JAMA, and the Cochrane Library until February 1, 2024. We aimed to analyze the metabolic advantages of bariatric surgery, focusing on its function in treating hyperuricemia and lowering the risk of associated disorders. Our review elaborates on factors contributing to decreased serum uric acid levels after bariatric surgery, such as alterations in renal function, insulin sensitivity, and inflammatory markers.
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Affiliation(s)
- Subodh Bashyal
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, CHN
| | - Shen Qu
- Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, CHN
- Shanghai Center of Thyroid Diseases, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, CHN
- SinoUnited Health, Endocrinology, Metabolism and Thyroid Center, Shanghai, CHN
| | - Manoj Karki
- Department of Internal Medicine, Endocrinology and Metabolism, Universal College of Medical Sciences, Tribhuvan University, Bhairahawa, NPL
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23
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Parveen S, Singh Sodhi J, Dhar N, Nazir S, Sharma A, Mir TA, Acharya K, Khan MA, Gulzar GM, Shah AH, Yattoo GN, Raina KS. Increase in acute pancreatitis, especially gallstone related, as the cause for emergency admissions: Temporal trend from Kashmir, India. Indian J Gastroenterol 2024:10.1007/s12664-023-01509-7. [PMID: 38446349 DOI: 10.1007/s12664-023-01509-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 12/19/2023] [Indexed: 03/07/2024]
Abstract
BACKGROUND The incidence of acute pancreatitis is increasing globally. Gallstones (GS) and ascariasis are the major causes for acute pancreatitis in the Kashmiri population. In recent years, we have observed an increase in the admission rate of acute pancreatitis. Many patients who present first time as gallstone pancreatitis have asymptomatic gallstones. We aimed at studying the etiology and yearly admission rate of acute pancreatitis with main focus on gallstone pancreatitis and the contribution of asymptomatic gallstones. METHODS This was a hospital-based, prospective, observational study from January 2015 to December 2019 for a period of five years. Patients of acute pancreatitis were evaluated for etiology and yearly admission rate. Patients of gallstone pancreatitis were evaluated in terms of clinical profile, risk factors, nature (symptomatic/asymptomatic, known/unknown gallstones), size of stones, treatment and outcome in terms of severity and mortality. The data was analyzed by Statistical Package for the Social Sciences (SPSS) version 20.0, as mean (SD), frequencies and percentages. RESULTS As many as 702 (8.5%) patients of acute pancreatitis were admitted among 8245 gastrointestinal emergencies in five years. The yearly admission rate of acute pancreatitis was 5.6%, 7.3%, 8.7%, 9.5% and 10.3%, respectively (p = 0.013). Gallstones, Ascariasis, alcohol and idiopathic acute pancreatitis were 47.7%, 6.9%, 1.2% and 33.7%, respectively. Gallstone pancreatitis increased from 31% in 2015 to 52.4% in 2019 (p = 0.045) and ascariasis-related acute pancreatitis declined from 14.4% to 1.6% (p = 0.034). Asymptomatic gallstones constituted 87.7% of cases. Known/unknown asymptomatic gallstones and symptomatic gallstones were 24.4%, 63.2% and 12.2%, respectively. Gallstones < 5 mm and > 5 mm were76.1% and 23.8% respectively (p = 0.027). Cholecystectomy rate in index admission was 4.7%. Mild, moderate and severe gallstone pancreatitis was 60.2%, 18.8% and 20.8%, respectively. Mortality in gallstone pancreatitis was 10.4%. CONCLUSION The incidence of acute pancreatitis is increasing due to gallstone pancreatitis. Ascariasis-related acute pancreatitis has declined. There is significant contribution of asymptomatic gallstones in patients who present for the first time as acute pancreatitis. Small gallstones < 5 mm are likely to be the risk factors for gallstone pancreatitis.
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Affiliation(s)
- Shaheena Parveen
- Department of Gastroenterology, Sheri-I-Kashmir Institute of Medical Sciences, Srinagar, 190 011, India
| | - Jaswinder Singh Sodhi
- Department of Gastroenterology, Sheri-I-Kashmir Institute of Medical Sciences, Srinagar, 190 011, India.
| | - Neeraj Dhar
- Department of Gastroenterology and Hepatology, Sarvodya Hospital, Faridabad, 121 006, India
| | - Shaheen Nazir
- Department of Gastroenterology, Sheri-I-Kashmir Institute of Medical Sciences, Srinagar, 190 011, India
| | - Ankush Sharma
- Department of Gastroenterology, Sheri-I-Kashmir Institute of Medical Sciences, Srinagar, 190 011, India
| | - Tariq Abdullah Mir
- Department of Gastroenterology, Sheri-I-Kashmir Institute of Medical Sciences, Srinagar, 190 011, India
| | - Kalpana Acharya
- Department of Gastroenterology, Sheri-I-Kashmir Institute of Medical Sciences, Srinagar, 190 011, India
| | - Mushtaq Ahmed Khan
- Department of Gastroenterology, Sheri-I-Kashmir Institute of Medical Sciences, Srinagar, 190 011, India
| | - Ghulam Mohd Gulzar
- Department of Gastroenterology, Sheri-I-Kashmir Institute of Medical Sciences, Srinagar, 190 011, India
| | - Altaf Hussain Shah
- Department of Gastroenterology, Sheri-I-Kashmir Institute of Medical Sciences, Srinagar, 190 011, India
| | | | - Kuldeep S Raina
- Department of Radiation Oncology, Sheri-I-Kashmir Institute of Medical Sciences, Srinagar, 190 011, India
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Oladimeji BM, Adebo OA. Antiobesity effect of healthy food crops and functional foods: A systematic review of their mechanisms. Food Sci Nutr 2024; 12:1380-1398. [PMID: 38455221 PMCID: PMC10916587 DOI: 10.1002/fsn3.3856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 11/02/2023] [Accepted: 11/07/2023] [Indexed: 03/09/2024] Open
Abstract
Diet is a modifiable risk factor in the prevention and management of obesity, and various foods have the potential to aid in obesity management by modulating different pathways involved in the disease's pathology. We performed a systematic review of literature, using CINAHL, PubMed, and Google Scholar, focusing on the antiobesity potential of foods crops and functional food products, and their mechanisms of action and clinical evidence. Sixty-four articles were identified, of which 41 investigated food crops, while 23 investigated functional products. Food crops, such as cereals, vegetables, fruits, mushrooms, seaweeds, legumes, herbs, spices, and cocoa seeds, have antiobesity effects through mechanisms such as altering the metabolism of glucolipids by inhibiting enzymes like α-amylase and α-glucosidase, stimulating the bioenergetics of thermogenic fat, modulating gut microbiota, and inhibiting lipogenesis and storage. In addition, developed functional teas, beverages, and yoghurt have antiobesity effects through similar or different mechanisms, such as enhancing energy expenditure and satiety, suppressing adipogenesis and lipolysis, improving glucose and lipid metabolism, and altering hormonal secretion. This review reemphasized the significance of food in the control of obesity, and highlights the distinct methods these explored foods exert their antiobesity effects. In conclusion, foods are safe and effective means of combating obesity without the side effects of conventional drugs, which can help inform dietary choices, assist professionals in providing more accurate advice, and also lead to better understanding of food and its effect on overall health of the public. This approach will eradicate global diseases, especially if more underutilized and indigenous food crops are extensively researched.
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Affiliation(s)
- Beatrice Mofoluwaso Oladimeji
- Food Innovation Research Group, Department of Biotechnology & Food Technology, Faculty of ScienceUniversity of JohannesburgJohannesburgSouth Africa
| | - Oluwafemi Ayodeji Adebo
- Food Innovation Research Group, Department of Biotechnology & Food Technology, Faculty of ScienceUniversity of JohannesburgJohannesburgSouth Africa
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25
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Watanabe H, Hoshide S, Kanegae H, Kario K. Prognosis of a malignant phenotype of obesity defined by a cardiac biomarker in hypertension: the Japan Morning Surge-Home Blood Pressure study. Hypertens Res 2024; 47:487-495. [PMID: 37857765 DOI: 10.1038/s41440-023-01468-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 07/28/2023] [Accepted: 09/26/2023] [Indexed: 10/21/2023]
Abstract
Obesity with increased high-sensitive cardiac troponin T (hs-cTnT) has been reported to be more likely to progress cardiovascular disease (CVD) events, which suggests that hs-cTnT may identify a "malignant" phenotype of obesity. We classified 3513 hypertensive patients from the Japan Morning Surge-Home Blood Pressure (J-HOP) study into groups based on body mass index (BMI) (normal weight: <25 kg/m2, overweight: 25-29.9 kg/m2, obesity: ≥30 kg/m2) and elevations in biomarker levels (hs-cTnT ≥3 ng/mL: 51.3%, 54.9%, 53.3%, and N-terminal pro-brain natriuretic peptide [NT-ProBNP] ≥55 pg/mL: 51.1%, 40.7%, 36.0% in each BMI category). We evaluated the independent and combined associations of BMI and each hs-cTnT/NT-proBNP or both with CVD events (fatal and nonfatal coronary artery disease, stroke, and hospitalized heart failure). During the mean 6.4 ± 3.9-year follow-up, 232 CVD events occurred. Obesity with elevated hs-cTnT was associated with a risk of CVD events compared to normal weight without elevated hs-cTnT (hazard ratio 3.22, 95% confidence interval: 1.83-5.68). A similar pattern of results was also observed across the status of obesity and elevated NT-proBNP. There was a significant interaction between hs-cTnT and CVD events according to the obesity status (p = 0.039), while this association was marginal in NT-proBNP (p = 0.060). The magnitude of the mediation of hs-cTnT for the association between obesity and CVD risk was 41.2%, and that for NT-proBNP was 8.1%. In this Japanese hypertensive population, the elevation of hs-cTnT identified obese patients at particularly high risk for developing CVD events, suggesting that hs-cTnT may identify a 'malignant' phenotype of obesity.
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Affiliation(s)
- Hiroaki Watanabe
- Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Satoshi Hoshide
- Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Hisoshi Kanegae
- Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
- Genki Plaza Medical Center for Health Care, Tokyo, Japan
| | - Kazuomi Kario
- Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan.
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McLaughlin AP, Lambert E, Milton R, Mariani N, Kose M, Nikkheslat N, Patsalos O, Ferraro L, Chamseddine G, Panagiotopoulos S, Chang A, Ramar S, Patel A, Rubino F, Mondelli V. Peripheral inflammation associated with depression and reduced weight loss: a longitudinal study of bariatric patients. Psychol Med 2024; 54:601-610. [PMID: 37652080 DOI: 10.1017/s0033291723002283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
Abstract
BACKGROUND Research implicates inflammation in the vicious cycle between depression and obesity, yet few longitudinal studies exist. The rapid weight loss induced by bariatric surgery is known to improve depressive symptoms dramatically, but preoperative depression diagnosis may also increase the risk for poor weight loss. Therefore, we investigated longitudinal associations between depression and inflammatory markers and their effect on weight loss and clinical outcomes in bariatric patients. METHODS This longitudinal observational study of 85 patients with obesity undergoing bariatric surgery included 41 cases with depression and 44 controls. Before and 6 months after surgery, we assessed depression by clinical interview and measured serum high-sensitivity C-reactive protein (hsCRP) and inflammatory cytokines, including interleukin (IL)-6 and IL-10. RESULTS Before surgery, depression diagnosis was associated with significantly higher serum hsCRP, IL-6, and IL-6/10 ratio levels after controlling for confounders. Six months after surgery, patients with pre-existing depression still had significantly higher inflammation despite demonstrating similar weight loss to controls. Hierarchical regression showed higher baseline hsCRP levels predicted poorer weight loss (β = -0.28, p = 0.01) but had no effect on depression severity at follow-up (β = -0.02, p = 0.9). Instead, more severe baseline depressive symptoms and childhood emotional abuse predicted greater depression severity after surgery (β = 0.81, p < 0.001; and β = 0.31, p = 0.001, respectively). CONCLUSIONS Depression was significantly associated with higher inflammation beyond the effect of obesity and other confounders. Higher inflammation at baseline predicted poorer weight loss 6 months after surgery, regardless of depression diagnosis. Increased inflammation, rather than depression, may drive poor weight loss outcomes among bariatric patients.
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Affiliation(s)
- Anna P McLaughlin
- Department of Psychological Medicine, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK
- National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and King's College London, London, UK
| | - Ellen Lambert
- Department of Psychological Medicine, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK
- National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and King's College London, London, UK
| | - Rebecca Milton
- Department of Psychological Medicine, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK
| | - Nicole Mariani
- Department of Psychological Medicine, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK
| | - Melisa Kose
- Department of Psychological Medicine, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK
| | - Naghmeh Nikkheslat
- Department of Psychological Medicine, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK
| | - Olivia Patsalos
- Department of Psychological Medicine, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK
- National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and King's College London, London, UK
| | - Luca Ferraro
- ASST Santi Paolo e Carlo, Azienda Socio Sanitaria Territorale Santi Paolo e Carlo, Milan, Italy
- Department of Metabolic & Bariatric Surgery, Diabetes & Nutritional Science Division, King's College Hospital, London, UK
| | - Ghassan Chamseddine
- Department of Metabolic & Bariatric Surgery, Diabetes & Nutritional Science Division, King's College Hospital, London, UK
| | - Spyros Panagiotopoulos
- Department of Metabolic & Bariatric Surgery, Diabetes & Nutritional Science Division, King's College Hospital, London, UK
| | - Avril Chang
- Department of Metabolic & Bariatric Surgery, Diabetes & Nutritional Science Division, King's College Hospital, London, UK
| | - Sasindran Ramar
- Department of Metabolic & Bariatric Surgery, Diabetes & Nutritional Science Division, King's College Hospital, London, UK
| | - Ameet Patel
- Department of Metabolic & Bariatric Surgery, Diabetes & Nutritional Science Division, King's College Hospital, London, UK
| | - Francesco Rubino
- Department of Metabolic & Bariatric Surgery, Diabetes & Nutritional Science Division, King's College Hospital, London, UK
| | - Valeria Mondelli
- Department of Psychological Medicine, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK
- National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and King's College London, London, UK
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27
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Danpanichkul P, Manosroi W, Nilsirisuk T, Tosukhowong T. Predictors of weight reduction effectiveness of SGLT2 inhibitors in diabetes mellitus type 2 patients. Front Endocrinol (Lausanne) 2024; 14:1251798. [PMID: 38327904 PMCID: PMC10849059 DOI: 10.3389/fendo.2023.1251798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 12/26/2023] [Indexed: 02/09/2024] Open
Abstract
Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a novel medication for treating type 2 diabetes (T2DM), which have the pleiotropic effect of weight reduction. This study aimed to evaluate clinical and biochemical predictors of effective weight reduction in T2DM patients who use various types of SGLT2i. Materials and methods A retrospective study was conducted with 289 adults diagnosed with T2DM who were first prescribed SGLT2i either as monotherapy or add-on therapy. The primary outcome was the identification of clinical and biochemical factors that can potentially induce meaningful weight reduction (>3% in 1 year) in T2DM patients while using SGLT2 inhibitors. The relationship between predictors and significant weight loss was assessed using logistic regression analysis, including adjustment for confounding factors. Results are presented as odds ratios (ORs) with a 95% confidence interval (CI). Results Among the 289 patients, 45.6% had significant weight loss following SGLT2i use. The significant clinical predictors were age >70 years old (OR 3.26, 95% CI 1.39-7.6, p=0.006), body mass index >25 kg/m2 (OR 1.02, 95% CI 1.01-1.05, p=0.049), and the use of sulfonylureas (OR 2.41, 95% CI 1.15-5.09, p=0.020). Additionally, the use of HCTZ showed significantly decreased odds of weight loss (OR 0.35, 95% CI 0.13-0.96, p=0.043). Conclusion This research highlights multiple clinical factors that potentially can predict meaningful weight loss in patients with T2DM who are treated with SGLT2i. These findings could facilitate the identification of patients who might benefit from the weight loss effects of SGLT2i.
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Affiliation(s)
- Pojsakorn Danpanichkul
- Immunology Unit, Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Worapaka Manosroi
- Division of Endocrinology, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand
- Clinical Epidemiology and Clinical Statistics Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | - Theetouch Tosukhowong
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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28
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Liu T, Wang J, Tong Y, Wu L, Xie Y, He P, Lin S, Hu X. Integrating network pharmacology and animal experimental validation to investigate the action mechanism of oleanolic acid in obesity. J Transl Med 2024; 22:86. [PMID: 38246999 PMCID: PMC10802007 DOI: 10.1186/s12967-023-04840-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 12/26/2023] [Indexed: 01/23/2024] Open
Abstract
BACKGROUND Obesity, a condition associated with the development of widespread cardiovascular disease, metabolic disorders, and other health complications, has emerged as a significant global health issue. Oleanolic acid (OA), a pentacyclic triterpenoid compound that is widely distributed in various natural plants, has demonstrated potential anti-inflammatory and anti-atherosclerotic properties. However, the mechanism by which OA fights obesity has not been well studied. METHOD Network pharmacology was utilized to search for potential targets and pathways of OA against obesity. Molecular docking and molecular dynamics simulations were utilized to validate the interaction of OA with core targets, and an animal model of obesity induced by high-fat eating was then employed to confirm the most central of these targets. RESULTS The network pharmacology study thoroughly examined 42 important OA targets for the treatment of obesity. The key biological processes (BP), cellular components (CC), and molecular functions (MF) of OA for anti-obesity were identified using GO enrichment analysis, including intracellular receptor signaling, intracellular steroid hormone receptor signaling, chromatin, nucleoplasm, receptor complex, endoplasmic reticulum membrane, and RNA polymerase II transcription Factor Activity. The KEGG/DAVID database enrichment study found that metabolic pathways, PPAR signaling pathways, cancer pathways/PPAR signaling pathways, insulin resistance, and ovarian steroidogenesis all play essential roles in the treatment of obesity and OA. The protein-protein interaction (PPI) network was used to screen nine main targets: PPARG, PPARA, MAPK3, NR3C1, PTGS2, CYP19A1, CNR1, HSD11B1, and AGTR1. Using molecular docking technology, the possible binding mechanism and degree of binding between OA and each important target were validated, demonstrating that OA has a good binding potential with each target. The molecular dynamics simulation's Root Mean Square Deviation (RMSD), and Radius of Gyration (Rg) further demonstrated that OA has strong binding stability with each target. Additional animal studies confirmed the significance of the core target PPARG and the core pathway PPAR signaling pathway in OA anti-obesity. CONCLUSION Overall, our study utilized a multifaceted approach to investigate the value and mechanisms of OA in treating obesity, thereby providing a novel foundation for the identification and development of natural drug treatments.
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Affiliation(s)
- Tianfeng Liu
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Waihuan East Road, Guangzhou, 510006, Guangdong, China
| | - Jiliang Wang
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Waihuan East Road, Guangzhou, 510006, Guangdong, China
| | - Ying Tong
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Waihuan East Road, Guangzhou, 510006, Guangdong, China
| | - Lele Wu
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Waihuan East Road, Guangzhou, 510006, Guangdong, China
| | - Ying Xie
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Waihuan East Road, Guangzhou, 510006, Guangdong, China
| | - Ping He
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Waihuan East Road, Guangzhou, 510006, Guangdong, China
| | - Shujue Lin
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Waihuan East Road, Guangzhou, 510006, Guangdong, China
| | - Xuguang Hu
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Waihuan East Road, Guangzhou, 510006, Guangdong, China.
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29
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Alhusseini N, Alsinan N, Almutahhar S, Khader M, Tamimi R, Elsarrag MI, Warar R, Alnasser S, Ramadan M, Omair A, Aouabdi S, Saleem R, Alabadi-Bierman A. Dietary trends and obesity in Saudi Arabia. Front Public Health 2024; 11:1326418. [PMID: 38274536 PMCID: PMC10808649 DOI: 10.3389/fpubh.2023.1326418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 12/19/2023] [Indexed: 01/27/2024] Open
Abstract
Introduction Dietary habits in Saudi Arabia have been shifting toward the Western diet, which is high in fat, salt, and sugar, leading to a high obesity rate. Different dietary strategies such as the Ketogenic Diet (KD), Intermittent Fasting (IF), Gluten Free Diet (GFD), and Calorie Restriction Diet (CRD) have shown an influential role in weight loss. This study aimed to compare trending diets and correlate different types of diet with obesity and lifestyle among adults in Saudi Arabia. Methods A cross-sectional study was performed on Saudis and non-Saudis over 18 years old. We used convenience sampling, an online questionnaire distributed via social media channels, including WhatsApp, LinkedIn, and Twitter. SPSS 28 software was applied for data analysis. The chi-square test was used to determine associations between different variables. Statistical significance was considered at a value of p less than 0.05. Results Most participants were females residing in the Eastern and Central regions of Saudi Arabia. Although most do not follow any dietary plan, they exhibited acceptable exercise and lifestyle. The minority of the study population followed different types of diet plans, such as KD, IF, and GFD. The purpose of most of the participants who have used these strategies was for weight loss but failed to sustain the dietary plan for more than 1 month. Conclusion Obesity remains a challenging issue in Saudi Arabia. Adherence to dietary regimes could help in controlling obesity. Increasing the awareness of the benefits of each dietary plan for health, choosing the appropriate one, and sustaining a balanced nutrition pattern.
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Affiliation(s)
| | - Nawra Alsinan
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | | | - Majd Khader
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Rawand Tamimi
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | | | - Rabah Warar
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Sara Alnasser
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Majed Ramadan
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Aamir Omair
- King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Sihem Aouabdi
- Ministry of National Guard, King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Rimah Saleem
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Alaa Alabadi-Bierman
- School of Public Health, Loma Linda University, Loma Linda, CA, United States
- University of California, Riverside, Riverside, CA, United States
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30
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Nayak N, Mukherjee T, Pattnaik A. Comprehensive Role of GDF15 in Inhibiting Adipogenesis and Hyperlipidemia, Enhancing Cardiovascular Health and Alleviating Inflammation in Metabolic Disorders. Curr Pharm Des 2024; 30:2387-2399. [PMID: 38934286 DOI: 10.2174/0113816128318741240611114448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Accepted: 05/21/2024] [Indexed: 06/28/2024]
Abstract
Growth Differentiation Factor 15 (GDF15) has emerged as a pivotal signaling molecule implicated in diverse physiological processes, spanning metabolic regulation, inflammation, and cardiovascular health. This study provides a comprehensive exploration of GDF15's multifaceted role, primarily focusing on its association with obesity-related complications and therapeutic potential. GDF15's involvement in energy homeostasis, specifically its regulation of body weight and appetite through hindbrain neuron activation and the GFRAL-RET signaling pathway, underscores its significance as an appetite-regulating hormone. GDF15's intricate modulation within adipose tissue dynamics in response to dietary changes and obesity, coupled with its influence on insulin sensitivity, highlights its critical role in metabolic health. The manuscript delves into the intricate crosstalk between GDF15 and pathways related to insulin sensitivity, macrophage polarization, and adipose tissue function, elucidating its potential as a therapeutic target for metabolic disorders associated with obesity. GDF15's association with chronic low-grade inflammation and its impact on cardiovascular health, particularly during hyperlipidemia and ischemic events, are explored. The intricate relationship between GDF15 and cardiovascular diseases, including its effects on endothelial function, cardiac hypertrophy, and heart failure, emphasizes its multifaceted nature in maintaining overall cardiovascular well-being. Challenges regarding the therapeutic application of GDF15, such as long-term safety concerns and ongoing clinical investigations, are discussed. Lastly, future research directions exploring GDF15's potential in addressing obesity-related complications and cardiovascular risks are proposed, highlighting its promising role as a therapeutic target in reshaping treatment strategies for obesity and associated health conditions.
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Affiliation(s)
- Nikita Nayak
- Department of Pharmaceutical Sciences and Technology, Division of Pharmacology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India
| | - Tuhin Mukherjee
- Department of Pharmaceutical Sciences and Technology, Division of Pharmacology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India
| | - Ashok Pattnaik
- Department of Pharmaceutical Sciences and Technology, Division of Pharmacology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India
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31
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Kim M, Lee S, Cho E, Hong KW, You SJ, Choi HJ. CETP and APOA2 polymorphisms are associated with weight loss and healthy eating behavior changes in response to digital lifestyle modifications. Sci Rep 2023; 13:21615. [PMID: 38062157 PMCID: PMC10703771 DOI: 10.1038/s41598-023-48823-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 11/30/2023] [Indexed: 12/18/2023] Open
Abstract
Response to digital healthcare lifestyle modifications is highly divergent. This study aimed to examine the association between single nucleotide polymorphism (SNP) genotypes and clinical efficacy of a digital healthcare lifestyle modification. We genotyped 97 obesity-related SNPs from 45 participants aged 18-39 years, who underwent lifestyle modification via digital cognitive behavioral therapy for obesity for 8 weeks. Anthropometric, eating behavior phenotypes, and psychological measures were analyzed before and after the intervention to identify their clinical efficacy. CETP (rs9939224) SNP significantly predict "super-responders" with greater body mass index (BMI) reduction (p = 0.028; GG - 2.91%, GT - 9.94%), while APOA2 (rs5082) appeared to have some potential for predicting "poor-responders" with lower BMI reduction (p = 0.005; AA - 6.17%, AG + 2.05%, and GG + 5.11%). These SNPs was also associated with significant differences in eating behavior changes, healthy diet proportions, health diet diversity, emotional and restrained eating behavior changes. Furthermore, classification using gene-gene interactions between rs9939224 and rs5082 significantly predicted the best response, with a greater decrease in BMI (p = 0.038; - 11.45% for the best response group (CEPT GT/TT × APOA2 AA) vs. + 2.62% for the worst response group (CEPT GG × APOA2 AG/GG)). CETP and APOA2 SNPs can be used as candidate markers to predict the efficacy of digital healthcare lifestyle modifications based on genotype-based precision medicine.Trial registration: NCT03465306, ClinicalTrials.gov. Registered March, 2018.
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Affiliation(s)
- Meelim Kim
- Department of Biomedical Science, Seoul National University College of Medicine, 28 Yungun-Dong, Chongno-Gu, Seoul, 110-799, Korea
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, CA, USA
- Center for Wireless and Population Health Systems, Calit2's Qualcomm Institute, University of California, San Diego, La Jolla, CA, USA
- The Design Lab, University of California, San Diego, La Jolla, CA, USA
| | - Seolha Lee
- Department of Biomedical Science, Seoul National University College of Medicine, 28 Yungun-Dong, Chongno-Gu, Seoul, 110-799, Korea
- Department of Global Medical Science, Sungshin Women's University, Seoul, Korea
| | - Eun Cho
- Department of Biomedical Science, Seoul National University College of Medicine, 28 Yungun-Dong, Chongno-Gu, Seoul, 110-799, Korea
| | | | | | - Hyung Jin Choi
- Department of Biomedical Science, Seoul National University College of Medicine, 28 Yungun-Dong, Chongno-Gu, Seoul, 110-799, Korea.
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Monsalve FA, Delgado-López F, Fernández-Tapia B, González DR. Adipose Tissue, Non-Communicable Diseases, and Physical Exercise: An Imperfect Triangle. Int J Mol Sci 2023; 24:17168. [PMID: 38138997 PMCID: PMC10743187 DOI: 10.3390/ijms242417168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 09/20/2023] [Accepted: 09/26/2023] [Indexed: 12/24/2023] Open
Abstract
The study of adipose tissue has received considerable attention due to its importance not just in maintaining body energy homeostasis but also in playing a role in a number of other physiological processes. Beyond storing energy, adipose tissue is important in endocrine, immunological, and neuromodulatory functions, secreting hormones that participate in the regulation of energy homeostasis. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favoring the secretion of deleterious adipocytokines that induce a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases and even some types of cancer. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity, with emphasis on hypocaloric diets and exercise. The aim of this review is to examine the pathophysiological mechanisms of obesity, considering the relationship among adipose tissue and two aspects that contribute positively or negatively to keeping a healthy body homeostasis, namely, exercise and noninfectious diseases. We conclude that the relationship of these aspects does not have homogeneous effects among individuals. Nevertheless, it is possible to establish some common mechanisms, like a decrease in pro-inflammatory markers in the case of exercise, and an increase in chronic inflammation in non-communicable diseases. An accurate diagnosis might consider the particular variables of a patient, namely their molecular profile and how it affects its metabolism, routines, and lifestyle; their underling health conditions; and probably even the constitution of their microbiome. We foresee that the development and accessibility of omics approaches and precision medicine will greatly improve the diagnosis, treatment, and successful outcomes for obese patients.
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Affiliation(s)
- Francisco A. Monsalve
- Department of Basic Biomedical Science, Faculty of Health Sciences, Universidad de Talca, Talca 3465548, Chile;
| | - Fernando Delgado-López
- Laboratories of Biomedical Research, Department of Preclinical Sciences, Faculty of Medicine, Universidad Católica del Maule, Talca 3466706, Chile;
| | | | - Daniel R. González
- Department of Basic Biomedical Science, Faculty of Health Sciences, Universidad de Talca, Talca 3465548, Chile;
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Dumlu Bilgin G, Büyükuslu N, Eyüpoğlu OE, Cumbul A. Co-administration of curcumin and polyamines in high-fat diet induced obese rats: Assessment of changes in serum polyamine levels and some tissue parameters. Prostaglandins Other Lipid Mediat 2023; 169:106784. [PMID: 37726052 DOI: 10.1016/j.prostaglandins.2023.106784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 09/15/2023] [Accepted: 09/16/2023] [Indexed: 09/21/2023]
Abstract
Obesity is a non-communicable chronic disease that continues to increase around the world. Recently, it has been shown that curcumin positively affects lipid, energy metabolism, and body weight change. Moreover, polyamines are aliphatic polycations, which can be found in all mammalian cells and foods and have been shown to prevent obesity through many different mechanisms. However, whether the co-administration of curcumin and polyamines has synergistic effects has yet to be clarified. Our study aimed to examine the effects of curcumin and polyamines on obesity and to assess the changes in serum polyamine levels and tissue parameters. 28 Sprague-Dawley male rats were fed a high-fat diet for 10 weeks to develop obesity, and then they were randomly divided into 4 groups as the control group (CONT), curcumin group (CUR), polyamine group (POL), curcumin and polyamine group (CUR+POL) and supplements were administered for 6 weeks. As a result, the lowest feed consumption in rats was recorded in the CUR+POL group, and the group with the lowest weight after supplements was the POL group, then the CUR+POL, CONT, and CUR groups, respectively. N-acetyl putrescine and GABA levels increased significantly after obesity development. The total histopathological score in fat, liver, and kidney tissues increased significantly in the CONT group. In the CUR+POL group, damage to the tissues was in the direction of recovery compared to the other groups, and the expression of NF-κB was significantly low. These results suggest that combined curcumin and polyamines may have protective effects.
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Affiliation(s)
- Gözde Dumlu Bilgin
- Yeditepe University, Faculty of Health Sciences, Department of Nutrition and Dietetics, İstanbul, Turkey.
| | - Nihal Büyükuslu
- Istanbul Medipol University, Faculty of Health Sciences, Department of Nutrition and Dietetics, İstanbul, Turkey
| | - Ozan Emre Eyüpoğlu
- Istanbul Medipol University, School of Pharmacy, Department of Biochemistry, İstanbul, Turkey
| | - Alev Cumbul
- Yeditepe University, Faculty of Medicine, Department of Histology and Embryology, İstanbul, Turkey
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Schmiedel O, Ivey M, Liu A, Murphy R. The New Zealand eating behavior questionnaire - Validation study for a novel assessment tool to describe actionable eating behavior traits. Appetite 2023; 191:107066. [PMID: 37852374 DOI: 10.1016/j.appet.2023.107066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 09/25/2023] [Accepted: 09/27/2023] [Indexed: 10/20/2023]
Abstract
Individualised management of obesity remains challenging and, to date, most treatment is based on clinical judgement. This study aimed to develop and validate a novel questionnaire-based tool to identify three pre-defined eating behavior (EB) traits, emotional eating, reduced satiety (constant hunger) and reduced satiation (feasters) that may predict selective medication response given their targeted actions. We recruited 977 individuals from a tertiary academic diabetes clinic to participate in this two-phase validation study. Participants self-reported weight management activities and were asked to self-assess their EB characteristics. The initial questionnaire included 42 visual analogue scale questions. In Phase I, 729 participants completed the questionnaire, including Māori (11.8%) and Pacific peoples (19.3%). After random division of the study sample, Exploratory Factor Analysis (EFA) confirmed a three-factor model as the best fit. Stepwise removal of items with inadequate factor loading retained 27 of 42 items, which accounted for 96% of the variance. Confirmatory Factor Analysis (CFA), performed on the second half of the sample, demonstrated good model fit with the final 27-item questionnaire. Internal consistency was high for factor (α = 0.82-0.95) and demographic subgroups, and similar to those obtained in the EFA. Test-retest reliability in a subset of 399 participants who repeated the questionnaire after a four-week interval (Phase II) showed moderate to good reliability. Participants classified into one of three EB types based on the highest median score among the factors. Test-retest reliability was robust for emotional eaters (71.25%) and constant hunger (68.9%). The correlation between aggregate EB score (sum of three EB scores) and BMI was significant (Spearman rho = 0.314, P = .0005). The questionnaire reliably identified three distinct EB traits, which may be informative for precision medicine applications for obesity management.
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Affiliation(s)
- Ole Schmiedel
- Department of Diabetes, Te Toka Tumai, Te Whatu Ora, New Zealand; University of Auckland, New Zealand.
| | | | - Amy Liu
- Department of Diabetes, Te Toka Tumai, Te Whatu Ora, New Zealand; University of Auckland, New Zealand
| | - Rinki Murphy
- Department of Diabetes, Te Toka Tumai, Te Whatu Ora, New Zealand; University of Auckland, New Zealand
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Dogan B, Dogan U, Gedik B, Turkmen B, Cakir RC, Demirer ME, Aslaner A. Optical coherence tomography angiography evaluation of optic disc and retinal vascular densities in obese patients. Photodiagnosis Photodyn Ther 2023; 44:103826. [PMID: 37797912 DOI: 10.1016/j.pdpdt.2023.103826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 09/19/2023] [Accepted: 10/02/2023] [Indexed: 10/07/2023]
Abstract
BACKGROUND To evaluate optic disc and retinal vascular densities in obese patients using optical coherence tomography angiography (OCTA). METHODS This study included 27 eyes from 27 obese patients with a body mass index (BMI) of ≥35 who were scheduled for bariatric surgery at the general surgery clinic and 26 eyes from 26 healthy individuals with a BMI of 18.5-24.9 kg/m2 who were of similar age and gender to the obese group. The macular vascular densities of the superficial and deep capillary plexuses (SCP and DCP, respectively), choriocapillaris flow area, optic disc peripapillary vascular density, and retinal thicknesses were evaluated using the OCTA device in obese patients and controls. RESULTS The mean age of the obese patients was 35.89 ± 10.93 years, and that of the controls was 32.31 ± 7.88 years (p = 0.199). The mean BMI values of the obese and control groups were 45.04 ± 6.89 kg/m2 and 23.19 ± 1.66 kg/m2, respectively (p < 0.0001). The whole, parafoveal, and perifoveal vascular density values of the SCP and those of the DCP were statistically significantly lower in the obese group than in the control group (p = 0.004, p = 0.011, p = 0.006, p = 0.036, p = 0.029, and p = 0.024, respectively). There was no significant difference between the two groups in terms of optic disc vascular density. Full retinal perifoveal thickness, full retinal perifoveal volume, inner retinal perifoveal thickness, and inner retinal perifoveal volume were statistically significantly lower in obese patients compared to the controls (p = 0.043, p = 0.042, p = 0.027, and p = 0.024, respectively). In addition, statistically significant negative correlations were found between BMI and the whole, parafoveal, and perifoveal vascular densities of the SCP and DCP and the whole vascular density values of the optic disc for all vessels and small vessels (p = 0.017, r = -0.327; p = 0.043, r = -0.280; p = 0.033, r = -0.293; p = 0.034, r = -0.291; p = 0.017, r = -0.327; p = 0.023, r = -0.311; p = 0.031, r = -0.296; and p = 0.047, r = -0.274, respectively). CONCLUSION We consider that the decrease in retinal vascular density and retinal thickness in obese patients is responsible for obesity-induced oxidative stress, increased inflammatory cytokines, and microvascular damage.
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Affiliation(s)
- Berna Dogan
- Department of Ophthalmology, Antalya Education and Research Hospital, University of Health Sciences, Antalya, Turkey.
| | - Ugur Dogan
- Department of General Surgery, Antalya Education and Research Hospital, University of Health Sciences, Antalya, Turkey
| | - Birumut Gedik
- Department of Ophthalmology, Antalya Serik State Hospital, Antalya, Turkey
| | - Berkay Turkmen
- Department of Ophthalmology, Antalya Education and Research Hospital, University of Health Sciences, Antalya, Turkey
| | - Remzi Can Cakir
- Department of General Surgery, Antalya Education and Research Hospital, University of Health Sciences, Antalya, Turkey
| | - Metin Eren Demirer
- Department of Ophthalmology, Antalya Education and Research Hospital, University of Health Sciences, Antalya, Turkey
| | - Arif Aslaner
- Department of General Surgery, Antalya Education and Research Hospital, University of Health Sciences, Antalya, Turkey
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Serrano N, Hyatt JPK, Houmard JA, Murgia M, Katsanos CS. Muscle fiber phenotype: a culprit of abnormal metabolism and function in skeletal muscle of humans with obesity. Am J Physiol Endocrinol Metab 2023; 325:E723-E733. [PMID: 37877797 PMCID: PMC10864022 DOI: 10.1152/ajpendo.00190.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 10/23/2023] [Accepted: 10/23/2023] [Indexed: 10/26/2023]
Abstract
The proportion of the different types of fibers in a given skeletal muscle contributes to its overall metabolic and functional characteristics. Greater proportion of type I muscle fibers is associated with favorable oxidative metabolism and function of the muscle. Humans with obesity have a lower proportion of type I muscle fibers. We discuss how lower proportion of type I fibers in skeletal muscle of humans with obesity may explain metabolic and functional abnormalities reported in these individuals. These include lower muscle glucose disposal rate, mitochondrial content, protein synthesis, and quality/contractile function, as well as increased risk for heart disease, lower levels of physical activity, and propensity for weight gain/resistance to weight loss. We delineate future research directions and the need to examine hybrid muscle fiber populations, which are indicative of a transitory state of fiber phenotype within skeletal muscle. We also describe methodologies for precisely characterizing muscle fibers and gene expression at the single muscle fiber level to enhance our understanding of the regulation of muscle fiber phenotype in obesity. By contextualizing research in the field of muscle fiber type in obesity, we lay a foundation for future advancements and pave the way for translation of this knowledge to address impaired metabolism and function in obesity.
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Affiliation(s)
- Nathan Serrano
- School of Life Sciences, Arizona State University, Tempe, Arizona, United States
| | - Jon-Philippe K Hyatt
- College of Integrative Sciences and Arts, Arizona State University, Tempe, Arizona, United States
| | - Joseph A Houmard
- Department of Kinesiology, Human Performance Laboratory, East Carolina University, Greenville, North Carolina, United States
| | - Marta Murgia
- Department of Biomedical Sciences, University of Padova, Padua, Italy
- Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany
| | - Christos S Katsanos
- School of Life Sciences, Arizona State University, Tempe, Arizona, United States
- Department of Physiology and Biomedical Engineering, Mayo Clinic-Arizona, Phoenix, Arizona, United States
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Xu Q, Ye J, Gong M, Zhang Y, Yuan Y, Zhao J. Theabrownin from Wuniuzao Dark Tea Regulates Hepatic Lipid Metabolism and Gut Microbiota in Mice Fed High-Fat Diet. Nutrients 2023; 15:4912. [PMID: 38068770 PMCID: PMC10708223 DOI: 10.3390/nu15234912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 11/21/2023] [Accepted: 11/22/2023] [Indexed: 12/18/2023] Open
Abstract
The search for functional foods with no side effects that can alleviate obesity has been a common trend. Wuniuzao dark tea could be a safe choice. This study aimed to explore whether theabrownin from Wuniuzao dark tea could regulate hepatic lipid metabolism and gut microbiota in mice fed a high-fat diet. In total, fifty 8-week-old male C57BL/6 mice were randomly divided into five treatment groups, including a normal control group, high-fat diet group, positive control group, low-dose theabrownin group, and high-dose theabrownin group. After a 9-week intervention, these mice were selected from each treatment group for sampling. The results showed that the body weight and epididymis fat weight of obese mice fed with theabrownin were decreased. Serum total triglycerides, total cholesterol, and low-density lipoprotein cholesterol, and activities of aspartate aminotransferase and alanine aminotransferase were also decreased. Protein and mRNA expression of fatty acid synthesis and lipid production-related genes of mice fed with theabrownin were downregulated. The gut microbiota composition in the theabrownin group was improved. The study indicated that theabrownin from Wuniuzao dark tea could achieve the liver protection and anti-obesity effects by regulating the Srebp lipid metabolism pathway and bile acid metabolism process, and improving the gut microbiota composition of mice.
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Affiliation(s)
| | | | | | | | | | - Jin Zhao
- Key Laboratory of Specialty Agri-Product Quality and Hazard Controlling Technology of Zhejiang Province, Institute of Food Nutrition and Quality Safety, College of Life Sciences, China Jiliang University, Hangzhou 310018, China; (Q.X.); (J.Y.); (M.G.); (Y.Z.); (Y.Y.)
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James DL, Larkey LK, Evans B, Sebren A, Goldsmith K, Ahlich E, Hawley NA, Kechter A, Sears DD. Mechanisms of improved body composition among perimenopausal women practicing Meditative Movement: a proposed biobehavioral model. Menopause 2023; 30:1114-1123. [PMID: 37788427 DOI: 10.1097/gme.0000000000002262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/05/2023]
Abstract
OBJECTIVES Weight gain and unfavorable body composition are prevalent among midlife/older women throughout menopause. These shifts may negatively impact health, well-being, and longevity. Efforts to attenuate weight and body composition changes are traditionally driven by manipulation of diet and/or exercise; however, sustained results are limited, possibly because the full spectrum of biobehavioral systems is not addressed by diet and exercise alone. We propose a biobehavioral model detailing mechanisms of body composition decline among perimenopausal women and the associated components of Meditative Movement (ie, tai chi, qigong, yoga) that address each of these factors. METHODS Based on our previous work and extensive review of the literature, we developed a multifactorial and multidimensional biobehavioral model including factors that most directly relate to body composition among perimenopausal women: 1) psychological (ie, stress and mood, mindfulness and self-compassion, body awareness), 2) behavioral (ie, sleep, physical activity, eating behaviors), and 3) physiological (ie, cortisol, estrogen). Relationships between each factor, Meditative Movement practice components, and predicted effects on body composition were explored in detail. RESULTS Our model describes select psychological, behavioral, and physiological factors, and potential mechanistic pathways of Meditative Movement practice driving improved changes in body composition and weight outcomes for perimenopausal women. CONCLUSIONS The proposed model details a novel, evidence-supported means to reduce the risk of deleterious shifts in body composition throughout perimenopause and menopause thereafter. We suggest that these changes may occur directly and/or indirectly through psychological, behavioral, and physiological mechanisms that facilitate the desired changes in body composition.
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Affiliation(s)
| | - Linda K Larkey
- From the Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ
| | - Bronwynne Evans
- From the Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ
| | - Ann Sebren
- College of Health Solutions, Arizona State University, Phoenix, AZ
| | - Kimberley Goldsmith
- Department of Biostatistics & Informatics, Institute of Psychiatry, King's College London, London, United Kingdom
| | - Erica Ahlich
- Department of Psychology, University of South Alabama, Mobile, AL
| | - Nanako A Hawley
- Department of Psychology, University of South Alabama, Mobile, AL
| | | | - Dorothy D Sears
- College of Health Solutions, Arizona State University, Phoenix, AZ
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Xu J, Wang S, Wu H, Chen D, Han J, Lin Q. Engineering a potent and long-acting GLP-1/Y 2 receptor dual agonist as a multi-agonist therapy for diabetes and obesity. Peptides 2023; 169:171073. [PMID: 37536423 DOI: 10.1016/j.peptides.2023.171073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/25/2023] [Accepted: 07/28/2023] [Indexed: 08/05/2023]
Abstract
Novel dual agonists for the glucagon-like peptide-1 (GLP-1) and Y2 receptor hold the potential for enhanced efficacy over GLP-1 receptor (GLP-1R) agonists in treating obesity and diabetes. In this study, we aimed to improve the stability and increase the drug development success rate of our previously identified GLP-1/Y2 receptor dual agonist, 6q. To achieve this, we first optimized the structure of the linker within 6q. Additionally, we explored various fatty acid albumin binders to further enhance the stability of 6q. These binders were mainly selected from approved or clinically developed GLP-1R agonists or GLP-1-based multi-agonists. Through this process, we were able to identify a lead peptide, xGLP/PYY-6, that exhibited comparable in vitro potency toward the GLP-1 and Y2 receptors as 6q but with significantly improved stability compared to 6q. In Kunming and DIO mice, xGLP/PYY-6 showed a comparable hypoglycemic effect to semaglutide, and a significantly better effect on inhibiting food intake than semaglutide. In a chronic study in DIO mice, xGLP/PYY-6 exhibited significant metabolic benefits, as reflected by regulation of lipid levels, improved glucose tolerance, weight loss, decreased hepatocellular vacuolation, and the reversal of steatosis effects caused by xGLP/PYY-6. These results indicate the potential of developing xGLP/PYY-6 as an antiobesity, lipid regulation, antisteatotic, and antidiabetic agent.
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Affiliation(s)
- Jing Xu
- Department of Pharmacy, Affiliated Lianyungang Hospital of Xuzhou Medical University/The First People's Hospital of Lianyungang, Lianyungang 222000, PR China
| | - Shuang Wang
- School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China
| | - Han Wu
- School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China
| | - De Chen
- School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China
| | - Jing Han
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning 530021, China; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning 530021, China.; School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China.
| | - Qisi Lin
- School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China.
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Maes B, Fayazpour F, Catrysse L, Lornet G, Van De Velde E, De Wolf C, De Prijck S, Van Moorleghem J, Vanheerswynghels M, Deswarte K, Descamps B, Vanhove C, Van der Schueren B, Vangoitsenhoven R, Hammad H, Janssens S, Lambrecht BN. STE20 kinase TAOK3 regulates type 2 immunity and metabolism in obesity. J Exp Med 2023; 220:e20210788. [PMID: 37347461 PMCID: PMC10287548 DOI: 10.1084/jem.20210788] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 03/31/2023] [Accepted: 06/02/2023] [Indexed: 06/23/2023] Open
Abstract
Healthy adipose tissue (AT) contains ST2+ Tregs, ILC2s, and alternatively activated macrophages that are lost in mice or humans on high caloric diet. Understanding how this form of type 2 immunity is regulated could improve treatment of obesity. The STE20 kinase Thousand And One amino acid Kinase-3 (TAOK3) has been linked to obesity in mice and humans, but its precise function is unknown. We found that ST2+ Tregs are upregulated in visceral epididymal white AT (eWAT) of Taok3-/- mice, dependent on IL-33 and the kinase activity of TAOK3. Upon high fat diet feeding, metabolic dysfunction was attenuated in Taok3-/- mice. ST2+ Tregs disappeared from eWAT in obese wild-type mice, but this was not the case in Taok3-/- mice. Mechanistically, AT Taok3-/- Tregs were intrinsically more responsive to IL-33, through higher expression of ST2, and expressed more PPARγ and type 2 cytokines. Thus, TAOK3 inhibits adipose tissue Tregs and regulates immunometabolism under excessive caloric intake.
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Affiliation(s)
- Bastiaan Maes
- Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Laboratory for Endoplasmic Reticulum Stress and Inflammation, VIB-UGent Center for Inflammation Research, Ghent, Belgium
| | - Farzaneh Fayazpour
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Laboratory for Endoplasmic Reticulum Stress and Inflammation, VIB-UGent Center for Inflammation Research, Ghent, Belgium
| | - Leen Catrysse
- Cellular and Molecular (Patho)Physiology, VIB-UGent Center for Inflammation Research, Ghent, Belgium
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
| | - Guillaume Lornet
- Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium
| | - Evelien Van De Velde
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Laboratory for Endoplasmic Reticulum Stress and Inflammation, VIB-UGent Center for Inflammation Research, Ghent, Belgium
| | - Caroline De Wolf
- Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Sofie De Prijck
- Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Justine Van Moorleghem
- Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Manon Vanheerswynghels
- Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Kim Deswarte
- Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Benedicte Descamps
- Department of Electronics and Information Systems, IBiTech-MEDISIP-Infinity Lab, Ghent University, Ghent, Belgium
| | - Christian Vanhove
- Department of Electronics and Information Systems, IBiTech-MEDISIP-Infinity Lab, Ghent University, Ghent, Belgium
| | - Bart Van der Schueren
- Department of Chronic Diseases and Metabolism, Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - Roman Vangoitsenhoven
- Department of Chronic Diseases and Metabolism, Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - Hamida Hammad
- Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Sophie Janssens
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Laboratory for Endoplasmic Reticulum Stress and Inflammation, VIB-UGent Center for Inflammation Research, Ghent, Belgium
| | - Bart N. Lambrecht
- Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Pulmonary Medicine, Erasmus University Medical Center Rotterdam, Rotterdam Netherlands
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James DL, Larkey LK, Goldsmith K, Evans B, Sebren A, Hawley NA. Well-being predictors of body composition and associated behavioral risk factors in midlife/older women participating in a meditative movement intervention: an exploratory analysis. J Clin Transl Sci 2023; 7:e194. [PMID: 37771415 PMCID: PMC10523288 DOI: 10.1017/cts.2023.621] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 07/28/2023] [Accepted: 08/22/2023] [Indexed: 09/30/2023] Open
Abstract
Introduction Greater than 40% of women are obese, a key risk factor for cardiometabolic, neurocognitive disease, mood disorders, and certain cancers. Obesity and unfavorable body composition can compromise physical and psychological health and well-being. Preliminary evidence demonstrates Meditative Movement (i.e., Tai Chi Easy) improves health outcomes and body composition among midlife/older women. This single-group pilot study explored relationships between well-being predictors related to body composition and associated behavioral risk factors in midlife/older women pre-to-post Tai Chi Easy intervention. Methods Eligible women 45-75 years old, participated in once-weekly 30-minute Tai Chi Easy classes over 8-weeks. Pre/post-intervention data included self-report surveys and on-site body composition. Multivariate linear regression models were fitted with putative predictor variables having correlations p-values of 0.20 or less with sleep quality and eating behaviors. Results Participants (N = 36) (M age = 53.7) were White (80.4%) and attended ≥ 4 years of college (70.6%). Analyses resulted in one independent variable per model as a predictor of the dependent variables of sleep quality and emotional eating. Results indicated: (1) stress explained 13.4% sleep quality variance (F (2, 20) = 2.71, p = 0.09) and (2) self-compassion explained 42.1% emotional eating variance (F (2, 31) = 12.54, p < .01). Conclusion Findings suggest stress and self-compassion partially explain variance in the dependent variables of sleep quality and emotional eating, both associated behavioral risk factors of body composition. Additional research may guide interventions to test efficacy and examine mediators to improve well-being predictors, body composition, and associated behavioral risk factors among midlife/older women.
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Affiliation(s)
- Dara L. James
- Edson College of Nursing and Health Innovation, Arizona State University, Tempe, AZ, USA
| | - Linda K. Larkey
- Edson College of Nursing and Health Innovation, Arizona State University, Tempe, AZ, USA
| | - Kimberley Goldsmith
- Department of Biostatistics & Informatics, Inst. Of Psychiatry, King’s College London, London, UK
| | - Bronwynne Evans
- Edson College of Nursing and Health Innovation, Arizona State University, Tempe, AZ, USA
| | - Ann Sebren
- College of Health Solutions, Arizona State University, Tempe, AZ, USA
| | - Nanako A. Hawley
- College of Arts and Sciences, University of South Alabama, Mobile, AL, USA
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Shi A, Deng J, Ma J, Yang L, Tantai X, Wang Q, Chang D, Wang J, Guo X, Lu X, Shi H. Prevalence and Risk Factors of Metabolic Dysfunction-Associated Fatty Liver Disease with Renal Insufficiency in Overweight/Obese Adults. Obes Facts 2023; 16:548-558. [PMID: 37640023 PMCID: PMC10697752 DOI: 10.1159/000533626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 08/10/2023] [Indexed: 08/31/2023] Open
Abstract
INTRODUCTION The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) with renal insufficiency in recent years and the association between MAFLD and renal insufficiency are not entirely clear, especially in overweight/obesity. The aim of this study was to analyze the prevalence and risk factors of MAFLD with renal insufficiency in overweight/obese adults. METHODS Individuals who attended checkup at the Second Affiliated Hospital of Xi'an Jiaotong University from 2016 to 2021 were included. The prevalence of MAFLD with renal insufficiency (estimated glomerular filtration rate ≤90 mL/min/1.73 m2) in overweight/obesity was estimated. Propensity score-matched analysis, univariate and multivariate analyses were used to determine the risk factors for MAFLD with renal insufficiency. RESULTS From 2016 to 2021, the prevalence of MAFLD in overweight/obesity reached its highest of 44.7% in 2017 and its lowest of 36.9% in 2018; and 33.9% in 2021 and 21.8% in 2019 is the highest and lowest prevalence of MAFLD with renal insufficiency, respectively. MAFLD was more common in men, old individuals, and persons with a higher body mass index (BMI) and was characterized by significant renal insufficiency. MAFLD with renal insufficiency was more common in women, old individuals, and persons with a higher BMI and was characterized by significant metabolic dysfunction and liver fibrosis. Multivariable analysis showed that BMI, uric acid, and fibrosis (evaluated with noninvasive liver fibrosis score [fibrosis-4]) were independent risk factors for MAFLD with renal insufficiency. CONCLUSION The prevalence of MAFLD with renal insufficiency in overweight/obese adults is quite high in the last 5 years. BMI, uric acid, and fibrosis are independent risk factors for MAFLD with renal insufficiency.
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Affiliation(s)
- Ameng Shi
- Department of Ultrasound, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jiang Deng
- Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Juan Ma
- Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Longbao Yang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xinxing Tantai
- Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Qian Wang
- Department of Health Management, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Danyan Chang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jinhai Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xiaoyan Guo
- Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xiaolan Lu
- Department of Gastroenterology, Pudong Hospital, Fudan University, Shanghai, China
| | - Haitao Shi
- Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Wirtz Baker JM, Pou SA, Niclis C, Haluszka E, Aballay LR. Non-traditional data sources in obesity research: a systematic review of their use in the study of obesogenic environments. Int J Obes (Lond) 2023:10.1038/s41366-023-01331-3. [PMID: 37393408 DOI: 10.1038/s41366-023-01331-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 06/01/2023] [Accepted: 06/21/2023] [Indexed: 07/03/2023]
Abstract
BACKGROUND The complex nature of obesity increasingly requires a comprehensive approach that includes the role of environmental factors. For understanding contextual determinants, the resources provided by technological advances could become a key factor in obesogenic environment research. This study aims to identify different sources of non-traditional data and their applications, considering the domains of obesogenic environments: physical, sociocultural, political and economic. METHODS We conducted a systematic search in PubMed, Scopus and LILACS databases by two independent groups of reviewers, from September to December 2021. We included those studies oriented to adult obesity research using non-traditional data sources, published in the last 5 years in English, Spanish or Portuguese. The overall reporting followed the PRISMA guidelines. RESULTS The initial search yielded 1583 articles, 94 articles were kept for full-text screening, and 53 studies met the eligibility criteria and were included. We extracted information about countries of origin, study design, observation units, obesity-related outcomes, environment variables, and non-traditional data sources used. Our results revealed that most of the studies originated from high-income countries (86.54%) and used geospatial data within a GIS (76.67%), social networks (16.67%), and digital devices (11.66%) as data sources. Geospatial data were the most utilised data source and mainly contributed to the study of the physical domains of obesogenic environments, followed by social networks providing data to the analysis of the sociocultural domain. A gap in the literature exploring the political domain of environments was also evident. CONCLUSION The disparities between countries are noticeable. Geospatial and social network data sources contributed to studying the physical and sociocultural environments, which could be a valuable complement to those traditionally used in obesity research. We propose the use of information available on the Internet, addressed by artificial intelligence-based tools, to increase the knowledge on political and economic dimensions of the obesogenic environment.
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Affiliation(s)
- Julia Mariel Wirtz Baker
- Health Sciences Research Institute (INICSA), National Council of Scientific and Technical Research (CONICET), Faculty of Medical Sciences, National University of Córdoba, Bv. De La Reforma, Ciudad Universitaria, Zip Code 5000, Córdoba, Argentina
- Human Nutrition Research Centre (CenINH), School of Nutrition, Faculty of Medical Sciences, National University of Córdoba, Bv. De La Reforma, Ciudad Universitaria, Zip Code 5000, Córdoba, Argentina
| | - Sonia Alejandra Pou
- Health Sciences Research Institute (INICSA), National Council of Scientific and Technical Research (CONICET), Faculty of Medical Sciences, National University of Córdoba, Bv. De La Reforma, Ciudad Universitaria, Zip Code 5000, Córdoba, Argentina
- Human Nutrition Research Centre (CenINH), School of Nutrition, Faculty of Medical Sciences, National University of Córdoba, Bv. De La Reforma, Ciudad Universitaria, Zip Code 5000, Córdoba, Argentina
| | - Camila Niclis
- Health Sciences Research Institute (INICSA), National Council of Scientific and Technical Research (CONICET), Faculty of Medical Sciences, National University of Córdoba, Bv. De La Reforma, Ciudad Universitaria, Zip Code 5000, Córdoba, Argentina
- Human Nutrition Research Centre (CenINH), School of Nutrition, Faculty of Medical Sciences, National University of Córdoba, Bv. De La Reforma, Ciudad Universitaria, Zip Code 5000, Córdoba, Argentina
| | - Eugenia Haluszka
- Health Sciences Research Institute (INICSA), National Council of Scientific and Technical Research (CONICET), Faculty of Medical Sciences, National University of Córdoba, Bv. De La Reforma, Ciudad Universitaria, Zip Code 5000, Córdoba, Argentina
- Human Nutrition Research Centre (CenINH), School of Nutrition, Faculty of Medical Sciences, National University of Córdoba, Bv. De La Reforma, Ciudad Universitaria, Zip Code 5000, Córdoba, Argentina
| | - Laura Rosana Aballay
- Human Nutrition Research Centre (CenINH), School of Nutrition, Faculty of Medical Sciences, National University of Córdoba, Bv. De La Reforma, Ciudad Universitaria, Zip Code 5000, Córdoba, Argentina.
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Schladitz K, Luppa M, Riedel-Heller SG, Loebner M. Effectiveness of internet-based and mobile-based interventions for adults with overweight or obesity experiencing symptoms of depression: a systematic review protocol. BMJ Open 2023; 13:e067930. [PMID: 37339836 DOI: 10.1136/bmjopen-2022-067930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/22/2023] Open
Abstract
INTRODUCTION Internet-based and mobile-based interventions (IMIs) provide innovative low-threshold and cost-effective prevention and self-management options for mental health problems complementary to standard treatment. The objective of this systematic review is to summarise the effectiveness and to critically evaluate studies on IMIs addressing comorbid depressive symptoms in adults with overweight or obesity. METHODS AND ANALYSIS The study authors will systematically search the databases MEDLINE, Cochrane Library, PsycINFO, Web of Science, Embase and Google Scholar (for grey literature) for randomised controlled trials (RCTs) of IMIs for individuals with overweight or obesity and comorbid depressive symptoms without restrictions on publication date (planned inception 1 June 2023 to 1 December 2023). Two reviewers will independently extract and evaluate data from studies eligible for inclusion by assessing quality of evidence and qualitatively synthesising results. Preferred Reporting Items for Systematic reviews Meta-Analyses (PRISMA) standards and the revised Cochrane Risk of Bias tool in RCTs (RoB 2) will be applied. ETHICS AND DISSEMINATION Ethical approval is not required as no primary data will be collected. Study results will be disseminated through publication in a peer-reviewed journal and presentations on conferences. PROSPERO REGISTRATION NUMBER CRD42023361771.
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Affiliation(s)
- Katja Schladitz
- Institute of Social Medicine, Occupational Health and Public Health, Leipzig University, Leipzig, Sachsen, Germany
| | - Melanie Luppa
- Institute of Social Medicine, Occupational Health and Public Health, Leipzig University, Leipzig, Sachsen, Germany
| | - Steffi G Riedel-Heller
- Institute of Social Medicine, Occupational Health and Public Health, Leipzig University, Leipzig, Sachsen, Germany
| | - Margrit Loebner
- Institute of Social Medicine, Occupational Health and Public Health, Leipzig University, Leipzig, Sachsen, Germany
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Zare Borzeshi E, Valizadeh M, Panahi MH, Khalili D, Mousavizadeh M, Mehrabi Y. Data-driven phenomapping for novel classification for cardiovascular outcomes compared with traditional obesity index: Tehran Lipid and Glucose Study. BMJ Open 2023; 13:e071011. [PMID: 37316323 DOI: 10.1136/bmjopen-2022-071011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/16/2023] Open
Abstract
OBJECTIVE This study aimed to propose a data-driven framework for classification of at-risk people for cardiovascular outcomes regarding obesity and metabolic syndrome. DESIGN A population-based prospective cohort study with a long-term follow-up. SETTING Data from the Tehran Lipid and Glucose Study (TLGS) were interrogated. PARTICIPANTS 12 808 participants of the TLGS cohort, aged ≥20 years who have followed for over 15 years were assessed. MAIN OUTCOME MEASURES Data for 12 808 participants, aged ≥20 years who have followed for over 15 years, collected through TLGS as a prospective, population-based cohort study, were analysed. Feature engineering followed by hierarchical clustering was used to determine meaningful clusters and novel endophenotypes. Cox regression was used to demonstrate the clinical validity of phenomapping. The performance of endophenotype compared with traditional classifications was evaluated by the value of Akaike information criterion/Bayesian information criterion. R software V.4.2 was employed. RESULTS The mean age was 42.1±14.9 years, 56.2% were female, 13.1%, 2.8% and 6.2% had experienced cardiovascular disease (CVD), CVD mortality and hard CVD, respectively. Low-risk cluster compared with the high risk had significant difference in age, body mass index, waist-to-hip ratio, 2 hours post load plasma glucose, triglyceride, triglycerides to high density lipoprotein ratio, education, marital status, smoking and the presence of metabolic syndrome. Eight distinct endophenotypes were detected with significantly different clinical characteristics and outcomes. CONCLUSION Phenomapping resulted in a novel classification of population with cardiovascular outcomes, which can, better, stratify individuals into homogeneous subclasses for prevention and intervention as an alternative of traditional methods solely based on either obesity or metabolic status. These findings have important clinical implications for a particular part of the Middle Eastern population for which it is a common practice to use tools/evidence derived from western populations with substantially different backgrounds and risk profiles.
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Affiliation(s)
- Elahe Zare Borzeshi
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Majid Valizadeh
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Hossein Panahi
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Khalili
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mostafa Mousavizadeh
- Heart Valve Disease Research Center, Rajaie Cardiovascular Medical and Research Center, Tehran, Iran
| | - Yadollah Mehrabi
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Mishra S, Kumar A, Kim S, Su Y, Singh S, Sharma M, Almousa S, Rather HA, Jain H, Lee J, Furdui CM, Ahmad S, Ferrario CM, Punzi HA, Chuang CC, Wabitsch M, Kritchevsky SB, Register TC, Deep G. A Liquid Biopsy-Based Approach to Isolate and Characterize Adipose Tissue-Derived Extracellular Vesicles from Blood. ACS NANO 2023; 17:10252-10268. [PMID: 37224410 PMCID: PMC10713009 DOI: 10.1021/acsnano.3c00422] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
Obesity is a major risk factor for multiple chronic diseases. Anthropometric and imaging approaches are primarily used to assess adiposity, and there is a dearth of techniques to determine the changes in adipose tissue (AT) at the molecular level. Extracellular vesicles (EVs) have emerged as a novel and less invasive source of biomarkers for various pathologies. Furthermore, the possibility of enriching cell or tissue-specific EVs from the biofluids based on their unique surface markers has led to classifying these vesicles as "liquid biopsies", offering valuable molecular information on hard-to-access tissues. Here, we isolated small EVs from AT (sEVAT) of lean and diet-induced obese (DIO) mice, identified unique surface proteins on sEVAT by surface shaving followed by mass spectrometry, and developed a signature of five unique proteins. Using this signature, we pulled out sEVAT from the blood of mice and validated the specificity of isolated sEVAT by measuring the expression of adiponectin, 38 adipokines on an array, and several adipose tissue-related miRNAs. Furthermore, we provided evidence of sEV applicability in disease prediction by characterizing sEVAT from the blood of lean and DIO mice. Interestingly, sEVAT-DIO cargo showed a stronger pro-inflammatory effect on THP1 monocytes compared to sEVAT-Lean and a significant increase in obesity-associated miRNA expression. Equally important, sEVAT cargo revealed an obesity-associated aberrant amino acid metabolism that was subsequently validated in the corresponding AT. Lastly, we show a significant increase in inflammation-related molecules in sEVAT isolated from the blood of nondiabetic obese (>30 kg/m2) individuals. Overall, the present study offers a less-invasive approach to characterize AT.
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Affiliation(s)
- Shalini Mishra
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Ashish Kumar
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Susy Kim
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Yixin Su
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Sangeeta Singh
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Mitu Sharma
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Sameh Almousa
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Hilal A Rather
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Heetanshi Jain
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Jingyun Lee
- Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, North Carolina 27157, United States
| | - Cristina M Furdui
- Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, North Carolina 27157, United States
- Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Sarfaraz Ahmad
- Laboratory of Translational Hypertension, Department of General Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Carlos M Ferrario
- Laboratory of Translational Hypertension, Department of General Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Henry A Punzi
- Punzi Medical Center, Punzi Institute of Medicine, Carrollton, Texas 75006, United States
- UT Southwestern Medical Center, Dallas, Texas, 75390, United States
| | - Chia-Chi Chuang
- Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Martin Wabitsch
- Department of Pediatrics and Adolescent Medicine, Center for Rare Endocrine Diseases, Ulm University Medical Centre, Ulm 89069, Germany
| | - Stephen B Kritchevsky
- Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
- Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Thomas C Register
- Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
- Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Gagan Deep
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
- Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, North Carolina 27157, United States
- Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
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Gonuguntla R, Ghali A, Prabhakar G, Momtaz D, Ahmad F, Slocum D, Kotzur T, Cushing T, Saydawi A, Wu C. The Effect of Obesity on Distal Radius Fractures: An Analysis from the NSQIP Database. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2023; 11:e5049. [PMID: 37305201 PMCID: PMC10256334 DOI: 10.1097/gox.0000000000005049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 04/10/2023] [Indexed: 06/13/2023]
Abstract
The rate and severity of obesity has risen over the past 40 years, and class III (formerly morbid) obesity presents additional sequelae. The effect of obesity on the incidence and recovery of hand and wrist fractures remains unclear. We sought to quantify the relationship between class III obesity and postoperative distal radius fracture (DRF) complications. Methods We performed a retrospective analysis of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database for surgical DRF patients more than 50 years old from 2015 to 2020. We then stratified patients into class III obese (BMI > 40) and compared the rates of postoperative complications to a control group with BMI less than 40. Results We included 10,022 patients (570 class III obese vs. 9,452 not class III obese). Patients with class III obesity had significantly increased odds of experiencing any complication (OR 1.906, p<0.001), adverse discharge (OR 2.618, p<0.001), delayed hospital stay of longer than three days (OR 1.91, p<0.001), and longer than seven days (OR 2.943, p<0.001) than controls. They also had increased odds of unplanned reoperation (OR 2.138, p = 0.026) and readmission (OR 2.814, p < 0.001) than non-class III obese patients. Class III obese patients had a significantly longer average operation time (79.5 min vs. 72.2 min, p < 0.001). They also spent more time in the hospital postoperatively (0.86 days vs. 0.57 days, p = 0.001). Conclusion Class III obese patients undergoing DRF repair are more likely to experience postoperative complications than non-class III obese patients.
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Affiliation(s)
- Rishi Gonuguntla
- From the UT Health San Antonio, Department of Orthopaedics, San Antonio, Tex
| | - Abdullah Ghali
- Baylor College of Medicine, Department of Orthopaedics, Houston, Tex
| | - Gautham Prabhakar
- From the UT Health San Antonio, Department of Orthopaedics, San Antonio, Tex
| | - David Momtaz
- From the UT Health San Antonio, Department of Orthopaedics, San Antonio, Tex
| | - Farhan Ahmad
- Rush University Medical Center, Department of Orthopaedics, Chicago, Ill
| | - Dean Slocum
- From the UT Health San Antonio, Department of Orthopaedics, San Antonio, Tex
| | - Travis Kotzur
- From the UT Health San Antonio, Department of Orthopaedics, San Antonio, Tex
| | - Tucker Cushing
- Baylor College of Medicine, Department of Orthopaedics, Houston, Tex
| | - Adnan Saydawi
- Damascus University College of Medicine, Damascus, Syrian Arab Republic
| | - Chia Wu
- Baylor College of Medicine, Department of Orthopaedics, Houston, Tex
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Kumar S, Chhimwal J, Kumar S, Singh R, Patial V, Purohit R, Padwad YS. Phloretin and phlorizin mitigates inflammatory stress and alleviate adipose and hepatic insulin resistance by abrogating PPARγ S273-Cdk5 interaction in type 2 diabetic mice. Life Sci 2023; 322:121668. [PMID: 37023949 DOI: 10.1016/j.lfs.2023.121668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/31/2023] [Accepted: 04/03/2023] [Indexed: 04/08/2023]
Abstract
AIMS The rising prevalence of type 2 diabetes mellitus (T2DM) and accompanying insulin resistance is alarming globally. Natural and synthetic agonists of PPARγ are potentially attractive candidates for diabetics and are known to efficiently reverse adipose and hepatic insulin resistance, but related side effects and escalating costs are the causes of concern. Therefore, targeting PPARγ with natural ligands is advantageous and promising approach for the better management of T2DM. The present research aimed to assess the antidiabetic potential of phenolics Phloretin (PTN) and Phlorizin (PZN) type 2 diabetic mice. MAIN METHODS In silico docking was performed to check the effect of PTN and PZN on PPARγ S273-Cdk5 interactions. The docking results were further validated in preclinical settings by utilizing a mice model of high fat diet-induced T2DM. KEY FINDINGS Computational docking and further MD-simulation data revealed that PTN and PZN inhibited the activation of Cdk5, thereby blocking the phosphorylation of PPARγ. Our in vivo results further demonstrated that PTN and PZN administration significantly improved the secretory functions of adipocytes by increasing adiponectin and reducing inflammatory cytokine levels, which ultimately reduced the hyperglycaemic index. Additionally, combined treatment of PTN and PZN decreased in vivo adipocyte expansion and increased Glut4 expression in adipose tissues. Furthermore, PTN and PZN treatment reduced hepatic insulin resistance by modulating lipid metabolism and inflammatory markers. SIGNIFICANCE In summary, our findings strongly imply that PTN and PZN are candidates as nutraceuticals in the management of comorbidities related to diabetes and its complications.
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Affiliation(s)
- Shiv Kumar
- Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, H.P., India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, U.P., India
| | - Jyoti Chhimwal
- Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, H.P., India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, U.P., India
| | - Suresh Kumar
- Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, H.P., India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, U.P., India
| | - Rahul Singh
- Structural Bioinformatics Lab, Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, H.P., India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, U.P., India
| | - Vikram Patial
- Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, H.P., India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, U.P., India
| | - Rituraj Purohit
- Structural Bioinformatics Lab, Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, H.P., India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, U.P., India.
| | - Yogendra S Padwad
- Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, H.P., India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, U.P., India.
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Vizitiu E, Constantinescu M. Study on the determination of the body and mental state of adult age patients. BALNEO AND PRM RESEARCH JOURNAL 2023. [DOI: 10.12680/balneo.2023.536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2023] Open
Abstract
Our study comes from the desire to highlight certain problems faced by adulthood, as well as the awareness of practicing physical exercise in water and on land, in order to combat them. Hypothesis of the work; it is assumed that through a thorough study in terms of body composition and mental status of patients of adult age, we will identify some problems that arise during this period of life and at the same time we will be able to develop truthful programs by applying physical means. The purpose of our work consists in highlighting the main problems of normoponderality and mental status on the patients subjected to the study by applying various tests that will highlight these aspects. Objectives of the study: Identification of body composition and mental status of adult patients; Patients' awareness of the normoponderality and mental problems arising from the applied tests; Promoting physical activities on land and in water, in adulthood. The result of questioning the subjects subjected to the study on the evaluation of the mental status revealed the fact that they have a temporal, spatial orientation, an adequate memory and attention, as well as a reading-writing and copying capacity corresponding to the age, and the determination of the body composition was achieved with the help of the "Tanita" device through which it was found an average of the group of subjects of 43.13% fat, 25,80 % muscle mass, 6,83 % bone mass, and water 42,22 %.
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Affiliation(s)
- Elena Vizitiu
- "Stefan cel Mare" University of Suceava, Suceava, Romania
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Núñez S, Moliner C, Valero MS, Mustafa AM, Maggi F, Gómez-Rincón C, López V. Antidiabetic and anti-obesity properties of a polyphenol-rich flower extract from Tagetes erecta L. and its effects on Caenorhabditis elegans fat storages. J Physiol Biochem 2023:10.1007/s13105-023-00953-5. [PMID: 36961724 DOI: 10.1007/s13105-023-00953-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 02/27/2023] [Indexed: 03/25/2023]
Abstract
Diabetes mellitus (DM) is a metabolic disease characterized by a high blood sugar level that can cause severe complications to the organism or even death when not treated. However, certain dietary habits and foods may have beneficial effects on this condition. A polyphenolic-rich extract (containing hyperoside, isoquercitrin, quercetin, ellagic acid, and vanillic acid) of Tageres erecta L. (T. erecta) was obtained from yellow and orange flowers using an ethanolic Soxhlet extraction. These extracts were screened for antidiabetic and anti-obesity properties using in vitro and in vivo procedures. The capacity to inhibit the enzymes lipase and α-glucosidase, as well as the inhibition of advance glycation end-products (AGEs) was tested in vitro. Caenorhabditis elegans (C. elegans) was used as an obesity in vivo model to assess extracts effects on fat accumulation using the wild-type strain N2 and a mutant with no N3 fatty acid desaturase activity BX24. Extracts from both cultivars (yellow and orange) T. erecta presented in vitro inhibitory activity against the enzymes lipase and α-glucosidase, showing lower IC50 values than acarbose (control). They also showed important activity in preventing AGEs formation. The polyphenol-rich matrices reduced the fat content of obese worms in the wild-type strain (N2) down to levels of untreated C. elegans, with no significant differences found between negative control (100% reduction) and both tested samples (p < 0.05). Meanwhile, the fat reduction was considerably lower in the BX24 mutants (fat-1(wa-9)), suggesting that N3 fatty acid desaturase activity could be partially involved in the T. erecta flower effect. Our findings suggested that polyphenols from T. erecta can be considered candidate bioactive compounds in the prevention and improvement of metabolic chronic diseases such as obesity and diabetes.
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Affiliation(s)
- Sonia Núñez
- Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, Villanueva de Gállego, Zaragoza, Spain
| | - Cristina Moliner
- Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, Villanueva de Gállego, Zaragoza, Spain
| | - Marta Sofía Valero
- Department of Pharmacology, Physiology and Legal and Forensic Medicine, Universidad de Zaragoza, Zaragoza, Spain
- Instituto Agroalimentario de Aragón, IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain
| | - Ahmed M Mustafa
- Chemistry Interdisciplinary Project (ChIP), School of Pharmacy, University of Camerino, Camerino, Italy
- Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt
| | - Filippo Maggi
- Chemistry Interdisciplinary Project (ChIP), School of Pharmacy, University of Camerino, Camerino, Italy
| | - Carlota Gómez-Rincón
- Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, Villanueva de Gállego, Zaragoza, Spain.
- Instituto Agroalimentario de Aragón, IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain.
| | - Víctor López
- Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, Villanueva de Gállego, Zaragoza, Spain
- Instituto Agroalimentario de Aragón, IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain
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