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Nishida N, Sugimoto S, Miyagaki S, Cho C, Konishi M, Goda T, Yamaguchi M, Kawabe Y, Morimoto H, Kusuyama J, Okamura T, Hamaguchi M, Mori J, Nakajima H, Fukui M, Iehara T. Anti-inflammatory effect of Angiotensin 1-7 in white adipose tissue. Adipocyte 2025; 14:2449027. [PMID: 39803918 PMCID: PMC11730366 DOI: 10.1080/21623945.2024.2449027] [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: 08/19/2024] [Revised: 12/08/2024] [Accepted: 12/29/2024] [Indexed: 01/16/2025] Open
Abstract
Obesity is a global health concern that promotes chronic low-grade inflammation, leading to insulin resistance, a key factor in many metabolic diseases. Angiotensin 1-7 (Ang 1-7), a component of the renin-angiotensin system (RAS), exhibits anti-inflammatory effects in obesity and related disorders, though its mechanisms remain unclear. In this study, we examined the effect of Ang 1-7 on inflammation of white adipose tissue (WAT) in dietary-induced obese mice. Monocyte chemoattractant protein-1 (MCP-1) produced by white adipocytes and tumour necrosis factor-α (TNF-α) produced by macrophages are pro-inflammatory cytokines and interact to form a pathogenic loop to exacerbate obesity-induced inflammation. We found that Ang 1-7 reduced MCP-1 and TNF-α gene expressions and the number of crown-like structures, which are histological hallmarks of the pro-inflammatory process, in visceral epididymal WAT (eWAT) and reduced circulating MCP-1 and TNF-α levels, accompanied by improvement in insulin resistance, in dietary-induced obese mice. Furthermore, Ang 1-7 reduced MCP-1 and TNF-α secretions in 3T3-L1 white adipocytes and RAW 264.7 macrophages, respectively, which are in vitro experimental models mimicking obesity condition. Our results suggest that Ang 1-7 directly acts on WAT to mitigate obesity-induced inflammation. Thus, this study provides novel insights into the underlying mechanism of anti-obesity effects of Ang 1-7.
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Affiliation(s)
- Nozomi Nishida
- Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Satoru Sugimoto
- Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Satoshi Miyagaki
- Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Chiharu Cho
- Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Madoka Konishi
- Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeshi Goda
- Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Mihoko Yamaguchi
- Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yasuhiro Kawabe
- Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hidechika Morimoto
- Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Joji Kusuyama
- Department of Biosignals and Inheritance, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan
| | - Takuro Okamura
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Jun Mori
- Division of Pediatric Endocrinology, Metabolism and Nephrology, Children’s Medical Center, Osaka City General Hospital, Osaka, Japan
| | - Hisakazu Nakajima
- Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tomoko Iehara
- Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Zhao H, Jiang M, Wang W, Tao Z, Wang X, Chai Y, Han Y, Liu Q, Chen Y, Yue J, Qi Y, Li X, Ma J, Pu J. Subclinical myocardial work impairment in non-diabetic overweight and obese individuals: Impact of cardiometabolic traits. Int J Cardiol 2025; 433:133321. [PMID: 40294804 DOI: 10.1016/j.ijcard.2025.133321] [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: 03/06/2025] [Revised: 04/12/2025] [Accepted: 04/24/2025] [Indexed: 04/30/2025]
Abstract
BACKGROUND Early detection of cardiac impairment in overweight and obesity is essential for early preventive strategies against heart failure. Myocardial work is a novel echocardiographic parameter that incorporates left ventricular afterload into global longitudinal strain analysis. This study aimed to: 1) assess subclinical alterations of myocardial work among non-diabetic overweight and obese individuals with normal left ventricular ejection fraction (LVEF); 2) investigate the impact of cardiometabolic traits on these alterations; and 3) determine the correlation between myocardial work and myocardial tissue characteristics. METHODS In the prospective EARLY-MYO-OBESITY-II study (NCT04933188), we enrolled 150 non-diabetic participants, including 50 obese individuals (BMI ≥ 30 kg/m2), 50 age- and gender-matched overweight individuals (BMI 25-30 kg/m2), and 50 healthy lean controls (BMI < 25 kg/m2). Non-invasive myocardial work was calculated from two-dimensional speckle-tracking echocardiography and cuff blood pressure, while myocardial fibrosis was assessed using extracellular volume fraction (ECV) and native T1 value from cardiac magnetic resonance imaging. RESULTS Global work index (GWI) and constructive work (GCW) were decreased in the obese participants compared with the overweight and control groups. Both overweight and obese groups exhibited elevated global wasted work (GWW) and reduced global work efficiency (GWE). In multivariate regression analysis, elevated Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values were independently associated with reduced GWI and GCW (β = -89.953 and -121.191, respectively). The overweight and obese groups showed elevated ECV and native T1 compared to the control group. GWW and GWE were significantly correlated with ECV (Spearman's Rho 0.516 and -0.547, respectively) and demonstrated superior predictive value for myocardial fibrosis (AUC = 0.86 and 0.82, respectively) compared to global longitudinal strain (AUC = 0.58). CONCLUSIONS Myocardial work is impaired in non-diabetic overweight and obese individuals, even with preserved LVEF. Insulin resistance is significantly and independently associated with myocardial work, highlighting the importance of targeting individuals with insulin resistance to reduce heart failure risk. Non-invasive myocardial work may serve as an image marker for detecting early cardiac fibrosis.
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Affiliation(s)
- Hang Zhao
- Department of Cardiology, Ren Ji Hospital, State Key Laboratory for Oncogenes and Related Genes, School of Medicine, Shanghai Jiao Tong University; Shanghai 200127, China
| | - Meng Jiang
- Department of Cardiology, Ren Ji Hospital, State Key Laboratory for Oncogenes and Related Genes, School of Medicine, Shanghai Jiao Tong University; Shanghai 200127, China.
| | - Wei Wang
- Department of Cardiology, Ren Ji Hospital, State Key Laboratory for Oncogenes and Related Genes, School of Medicine, Shanghai Jiao Tong University; Shanghai 200127, China
| | - Zhengyu Tao
- Department of Cardiology, Ren Ji Hospital, State Key Laboratory for Oncogenes and Related Genes, School of Medicine, Shanghai Jiao Tong University; Shanghai 200127, China
| | - Xu Wang
- Department of Cardiology, Ren Ji Hospital, State Key Laboratory for Oncogenes and Related Genes, School of Medicine, Shanghai Jiao Tong University; Shanghai 200127, China
| | - Yezi Chai
- Department of Cardiology, Ren Ji Hospital, State Key Laboratory for Oncogenes and Related Genes, School of Medicine, Shanghai Jiao Tong University; Shanghai 200127, China
| | - Yuchi Han
- Cardiovascular Division, The Ohio State Wexner Medical Center, Columbus, OH, United States of America
| | - Qiming Liu
- Department of Cardiology, Ren Ji Hospital, State Key Laboratory for Oncogenes and Related Genes, School of Medicine, Shanghai Jiao Tong University; Shanghai 200127, China
| | - Yifan Chen
- Department of Cardiology, Ren Ji Hospital, State Key Laboratory for Oncogenes and Related Genes, School of Medicine, Shanghai Jiao Tong University; Shanghai 200127, China
| | - Jiang Yue
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Yicheng Qi
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Xinli Li
- State Key Laboratory for Innovation and Transformation of Luobing Theory, Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu, China
| | - Jing Ma
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
| | - Jun Pu
- Department of Cardiology, Ren Ji Hospital, State Key Laboratory for Oncogenes and Related Genes, School of Medicine, Shanghai Jiao Tong University; Shanghai 200127, China.
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Vargas MR, Ferreira MDR, Collins P, D'Alessandro ME. Astaxanthin obtained from freshwater crustaceans mitigates visceral adiposity by modulating adipose tissue lipogenesis and ameliorates dyslipidemia in high-sucrose diet fed rats. J Nutr Biochem 2025; 142:109924. [PMID: 40245956 DOI: 10.1016/j.jnutbio.2025.109924] [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: 01/27/2025] [Revised: 03/28/2025] [Accepted: 04/11/2025] [Indexed: 04/19/2025]
Abstract
The incidence of overweight and obesity continues to grow at alarming rates around the world. The search for foods with potential benefits in the prevention/treatment of overweight/obesity and related disorders has great relevance. The aim of this study was to evaluate the effect of astaxanthin (ASTX) from freshwater crustaceans (crabs) upon visceral adiposity, adipose tissue lipid metabolism disorders and dyslipidemia present in a Metabolic Syndrome rodent model. Male Wistar rats were fed for 90 days with 1 of 4 experimental diets: a-Reference group (RD) received a standard commercial rodent diet, b- High-sucrose diet (HSD) group received a HSD, c- RD+ASTX group received a standard commercial rodent diet plus ASTX, d- HSD+ASTX group received a HSD plus ASTX. The rats were given orally either ASTX (10 mg/kg body weight/day in sunflower oil) or only sunflower oil. Compared with HSD-fed rats, HSD+ASTX group had lower body weight gain (19%) and both reduced abdominal circumference (5%) and visceral adiposity index (5%). Energy intake was 24% lower at the middle of the experimental period. Epididymal adipocytes size and triglyceride (TG) content was reduced by 14%. Besides, fatty acid synthase, malic enzyme and glucose-6-phosphate dehydrogenase activities in epididymal adipose tissue were 43%, 28% and 38% lower respectively. These changes were accompanied by lower TG (25%) and cholesterol (27%) serum levels, atherogenic index (31%) and reduced Systolic (12%) and Diastolic (15%) blood pressure. The results show that ASTX could be a potential strategy to prevent/attenuate the incidence of metabolic risk factors such as overweight/adiposity and dyslipidemia.
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Affiliation(s)
- Matias Rodrigo Vargas
- Laboratorio de Estudio de Enfermedades Metabólicas relacionadas con la Nutrición. Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, 3000, Argentina
| | - María Del Rosario Ferreira
- Laboratorio de Estudio de Enfermedades Metabólicas relacionadas con la Nutrición. Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, 3000, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
| | - Pablo Collins
- Departamento de Acuicultura, COE INTA Ángel Gallardo (EEA Rafaela), Universidad Nacional del Litoral- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, Argentina
| | - María Eugenia D'Alessandro
- Laboratorio de Estudio de Enfermedades Metabólicas relacionadas con la Nutrición. Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, 3000, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
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Zambrano-Vásquez OR, Cortés-Camacho F, Castañeda-Sánchez JI, Aréchaga-Ocampo E, Valle-Velázquez E, Cabrera-Angeles JC, Sánchez-Gloria JL, Sánchez-Muñoz F, Arellano-Buendia AS, Sánchez-Lozada LG, Osorio-Alonso H. Update in non-alcoholic fatty liver disease management: role of sodium-glucose cotransporter 2 inhibitors. Life Sci 2025; 372:123638. [PMID: 40246191 DOI: 10.1016/j.lfs.2025.123638] [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: 12/18/2024] [Revised: 03/28/2025] [Accepted: 04/09/2025] [Indexed: 04/19/2025]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes without significant alcohol consumption. It is closely associated with sedentarism, hypercaloric diets, obesity, dyslipidemia, insulin resistance, type 2 diabetes mellitus, and genetic predisposition. NAFLD comprises a spectrum of liver disorders, from simple steatosis to non-alcoholic (NASH) and liver cirrhosis. The complex etiological mechanisms include oxidative stress, inflammation, apoptosis, and fibrosis; therefore, its management is challenging. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i), a class of antidiabetic drugs, have emerged as promising therapeutic agents due to their ability to improve key metabolic parameters, including obesity, dyslipidemia, insulin resistance, and hyperglycemia. This review explores the cellular mechanisms by which SGLT2i, either as monotherapy or combined with other treatments, modulate signaling pathways involved in lipid and carbohydrate metabolism. Additionally, we examine their effects on oxidative stress, inflammation, fibrosis, and apoptosis, which are critical drivers of NAFLD progression. This review is intended to summarize the multiple benefits of SGLT2 inhibitors and to educate healthcare providers on the therapeutic potential of these drugs in order to foster their incorporation into effective NAFLD management plans.
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Affiliation(s)
- Oscar R Zambrano-Vásquez
- Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Ciudad de México 04960, Mexico; Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, México City 14080, Mexico
| | - Fernando Cortés-Camacho
- Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Ciudad de México 04960, Mexico; Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, México City 14080, Mexico
| | - Jorge I Castañeda-Sánchez
- Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Unidad Xochimilco, México City 04960, Mexico
| | - Elena Aréchaga-Ocampo
- Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, México City 05348, Mexico
| | - Estefanía Valle-Velázquez
- Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, México City 14080, Mexico
| | - Juan C Cabrera-Angeles
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, Mexico
| | - José L Sánchez-Gloria
- Department of Internal Medicine, Division of Nephrology, Rush University Medical Center, Chicago, IL 60612, USA
| | - Fausto Sánchez-Muñoz
- Departamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, México City 14080, Mexico
| | - Abraham S Arellano-Buendia
- Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, México City 14080, Mexico
| | - Laura G Sánchez-Lozada
- Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, México City 14080, Mexico
| | - Horacio Osorio-Alonso
- Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, México City 14080, Mexico.
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Vratarić M, Teofilović A, Milutinović DV, Veličković N, Vučićević L, Đmura G, Djordjevic A. Changes in lipid metabolism in the visceral rather than the subcutaneous adipose tissue depot attenuate metabolic disturbances in obesity-resistant mice fed a high-fat diet. J Nutr Biochem 2025; 141:109912. [PMID: 40174754 DOI: 10.1016/j.jnutbio.2025.109912] [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: 09/12/2024] [Revised: 03/12/2025] [Accepted: 03/27/2025] [Indexed: 04/04/2025]
Abstract
Obesity is characterized by an enlargement of white adipose tissue caused by caloric excess. The depot-specific adaptation of white adipose tissue in individuals resistant to obesity despite a high-calorie diet is crucial for understanding the pathogenesis of obesity and related metabolic disorders. Our aim was to characterize the metabolic and morphological state of obesity resistance and to investigate depot-specific changes in signaling pathways in epididymal visceral (eVAT) and inguinal subcutaneous (iSAT) white adipose tissue of C57BL/6J male mice on a high-fat diet (60 kcal% fats). After 14 weeks, the mice were categorized as obese (at least 30% higher body mass compared to the control group) or obesity-resistant (weight gain below 30%). Biochemical and morphological parameters, as well as histology, and signaling pathways involved in lipid metabolism, inflammation, and insulin sensitivity were investigated in eVAT and iSAT. The results showed unaltered body, total VAT and iSAT mass in obesity-resistant mice despite increased caloric intake. Leptin levels and glucose homeostasis were improved in these animals compared to the obese mice. In both eVAT and iSAT of the obesity-resistant mice, adipocyte size and lipolytic capacity were retained at control levels, while compared to the obese mice, preserved capacity for adipogenesis, improved local insulin sensitivity and the absence of inflammation were observed only in the eVAT. In conclusion, metabolic adaptation of eVAT rather than iSAT may have a substantial impact on the maintenance of the obesity-resistant phenotype with fewer metabolic complications, which could contribute to the improvement of existing obesity therapies.
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Affiliation(s)
- Miloš Vratarić
- Department of Biochemistry, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Ana Teofilović
- Department of Biochemistry, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
| | - Danijela Vojnović Milutinović
- Department of Biochemistry, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Nataša Veličković
- Department of Biochemistry, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Ljubica Vučićević
- Department of Neurophysiology, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Goran Đmura
- Animal Facility, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Ana Djordjevic
- Department of Biochemistry, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
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Mohaghegh N, Iyer A, Wang E, Balajam NZ, Kang H, Akbari M, Barnhill MS, Khademhosseini A, Pearson RM, Hassani Najafabadi A. Apigenin-loaded nanoparticles for obesity intervention through immunomodulation and adipocyte browning. J Control Release 2025; 382:113670. [PMID: 40187647 DOI: 10.1016/j.jconrel.2025.113670] [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: 12/11/2024] [Revised: 03/04/2025] [Accepted: 03/27/2025] [Indexed: 04/07/2025]
Abstract
Obesity is characterized by a significant imbalance in adipose tissue macrophages (ATMs), shifting from anti-inflammatory M2 to pro-inflammatory M1 phenotypes, contributing to chronic low-grade inflammation and metabolic dysfunction. This study explores the potential of nanoparticle (NP)-mediated immunomodulation to address obesity-related inflammation, adipocyte browning, and metabolic dysfunction. Apigenin (Api), a natural compound with notable anti-inflammatory properties, was encapsulated within poly(lactic-co-glycolic acid) (PLGA) NPs (Api-NPs) for localized delivery to adipose tissues (ATs). Api-NPs demonstrated favorable physicochemical properties and sustained release profiles. In vitro, Api-NPs, increased M2 macrophage (MΦ) polarization, reduced inflammatory markers, and promoted adipocyte browning. In a high-fat diet (HFD)-induced obesity mouse model, Api-NP administration effectively modulated MΦ polarization and enhanced AT browning, leading to marked reductions in body weight and AT mass. Our findings indicate that Api-NP treatment mitigates obesity-related inflammation and promotes beneficial changes in AT composition and function. Importantly, histological evaluations confirmed the absence of toxicity in major organs, reinforcing the safety profile of this approach. These results position Api-NPs as a promising novel therapeutic strategy for obesity management, integrating immune modulation and localized drug delivery to address the complexities of obesity and its associated inflammatory processes.
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Affiliation(s)
- Neda Mohaghegh
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA
| | - Anjali Iyer
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA
| | - Ethan Wang
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
| | | | - Heemin Kang
- Materials Science and Engineering, Korea University, Seoul 02841, Republic of Korea
| | - Mohsen Akbari
- Laboratory for Innovations in MicroEngineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC, Canada
| | | | - Ali Khademhosseini
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA
| | - Ryan M Pearson
- Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
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7
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Juguilon C, Khosravi R, Radisic M, Wu JC. In Vitro Modeling of Interorgan Crosstalk: Multi-Organ-on-a-Chip for Studying Cardiovascular-Kidney-Metabolic Syndrome. Circ Res 2025; 136:1476-1493. [PMID: 40403116 DOI: 10.1161/circresaha.125.325497] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Revised: 04/23/2025] [Accepted: 04/24/2025] [Indexed: 05/24/2025]
Abstract
Cardiovascular-kidney-metabolic syndrome is a progressive disorder driven by perturbed interorgan crosstalk among adipose, liver, kidney, and heart, leading to multiorgan dysfunction. Capturing the complexity of human cardiovascular-kidney-metabolic syndrome pathophysiology using conventional models has been challenging. Multi-organ-on-a-chip platforms offer a versatile means to study underlying interorgan signaling at different stages of cardiovascular-kidney-metabolic syndrome and bolster clinical translation.
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Affiliation(s)
- Cody Juguilon
- Stanford Cardiovascular Institute (C.J., J.C.W.), Stanford University, Stanford, CA
- Division of Cardiovascular Medicine, Department of Medicine (C.J., J.C.W.), Stanford University, Stanford, CA
| | - Ramak Khosravi
- Toronto General Hospital Research Institute, University Health Network, Ontario, Canada (R.K., M.R.)
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC (R.K.)
| | - Milica Radisic
- Stanford Cardiovascular Institute (C.J., J.C.W.), Stanford University, Stanford, CA
- Toronto General Hospital Research Institute, University Health Network, Ontario, Canada (R.K., M.R.)
- Institute of Biomedical Engineering (M.R.)
- University of Toronto, Ontario, Canada (M.R.)
| | - Joseph C Wu
- Stanford Cardiovascular Institute (C.J., J.C.W.), Stanford University, Stanford, CA
- Division of Cardiovascular Medicine, Department of Medicine (C.J., J.C.W.), Stanford University, Stanford, CA
- Greenstone Biosciences, Palo Alto, CA (J.C.W.)
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8
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Elkanawati RY, Sumiwi SA, Levita J. The Effects of the Ethanol Extract of Allium Ascalonicum L. in High-Fat-High-Fructose-Induced Insulin Resistance Swiss-Webster Male Mice. J Exp Pharmacol 2025; 17:207-221. [PMID: 40395837 PMCID: PMC12091064 DOI: 10.2147/jep.s513301] [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: 01/13/2025] [Accepted: 04/09/2025] [Indexed: 05/22/2025] Open
Abstract
Background Insulin resistance (IR) is a condition where the body cannot respond properly to insulin, leading to elevated blood glucose and the development of type 2 diabetes mellitus (T2DM). The first-line anti-T2DM drug is metformin, however, it has shown adverse effects, challenging the search for alternative natural drugs. Plant flavonoids stimulate cellular glucose uptake, decrease hyperglycemia, and regulate key signaling pathways in glucose metabolism. Brebes shallots (Allium ascalonicum L.) are known to contain flavonoids and thus may have the potential to inhibit IR. Purpose To evaluate the effects of the ethanol extract of Brebes shallots in improving IR conditions. Methods Brebes shallots were collected from West Java, Indonesia. 500 g of the shallots were oven-dried and extracted using 70% ethanol for 3×24 h, the solvent was evaporated to a thick consistency, and the extract was abbreviated as EAA. The effects of EAA were studied in high-fat-high-fructose (HFHF)-induced Swiss-Webster male mice by performing the insulin tolerance test (ITT) and oral glucose tolerance test (OGTT), and the liver and pancreas index. The nutritional composition and quercetin levels in the extract were also determined. Results The extraction process yielded a 28.1% EAA. EAA reduces % weight gain, blood glucose levels in OGTT, and liver and pancreas index. EAA significantly improved insulin tolerance in the HFHF-induced mice (p < 0.05). Proximate analysis resulted in 3.92% ash, 0.12% fat, 13.45% protein, and 60.69% carbohydrate, while quercetin was at 0.0065%. Conclusion Allium ascalonicum L. extract may improve IR conditions as confirmed by its ability to increase the ITT value and reduce blood glucose levels. However, further studies are needed to confirm its role in alleviating metabolic disorders.
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Affiliation(s)
| | - Sri Adi Sumiwi
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia
| | - Jutti Levita
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia
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Yu H, Guo B, Miao Z, Chen C, Song Y, Yang J. A high-fat diet suppresses growth hormone synthesis and secretion by influencing the Vit D receptor and Pit1. Endocrine 2025:10.1007/s12020-025-04270-3. [PMID: 40369297 DOI: 10.1007/s12020-025-04270-3] [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: 02/07/2025] [Accepted: 04/30/2025] [Indexed: 05/16/2025]
Abstract
BACKGROUND A long-term high-fat diet (HFD) leads to excessive lipid deposition, which may cause many diseases, including NAFLD, diabetes, and thyroid dysfunction. In addition, HFD leads to a decrease in serum growth hormone (GH) levels to further increase lipid deposition and obesity. However, the mechanism of such reduction of GH has not been fully elucidated. METHODS Male Sprague-Dawley rats were fed a regular diet (CD) or a high-fat diet (HFD) for 29 weeks. GH synthesis and secretion were evaluated in pituitary and blood samples, respectively. An in vitro model was constructed by treating cultured cells with palmitic acid (PA). Vit D receptor (VDR) plasmids (OE-VDR), paricalcitol and VDR knockdown virus (sh-VDR) were used to overexpress or depress the activation of VDR during PA treatment of GH3 cells. The GH content, lipid content, and relevant expression of different molecules were measured in pituitary and cell samples. RESULTS A HFD decreased the levels of circulating GH and the expression of Gh in the anterior pituitary gland tissues of rats. In vitro, PA treatment decreased Pit1 and Gh expression in cultured GH3 cells. VDR expression was reduced in the rat pituitary tissues under HFD conditions and in PA-treated GH3 cells. The overexpression and knockdown of VDR increased and decreased the expression of Pit1 and Gh, respectively. Paricalcitol antagonized the decrease in the expression of Pit1 and Gh caused by PA treatment. CONCLUSIONS HFD induced lipid deposition in the pituitary may cause GH deficiency, and VDR - Pit1 may be at least partially involved in the process.
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Affiliation(s)
- Huimin Yu
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Key Laboratery of Endocine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Jinan, China
| | - Boning Guo
- Key Laboratery of Endocine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Jinan, China
- Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Zhiwei Miao
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Key Laboratery of Endocine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Jinan, China
| | - Chen Chen
- Endocrinology, SBMS, Faculty of Medicine, The University of Queensland, St Lucia, Qld, Australia
| | - Yongfeng Song
- Department of Endocrinology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
| | - Jianmei Yang
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
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10
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Verma M, Kalra S, Deepa M, Venkatesan U, Sharma N, Pradeepa R, Chauhan K, Singh O, Elangovan N, Aggarwal S, Kakkar R, Dhaliwal RS, Kaur T, Mohan V, Anjana RM. Understanding Epidemiology of Physical Activity and Sedentary Behaviour Among Adults in Haryana: Insights from the ICMR-INDIAB Study [ICMR-INDIAB-19]. Adv Ther 2025:10.1007/s12325-025-03200-z. [PMID: 40358896 DOI: 10.1007/s12325-025-03200-z] [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: 10/22/2024] [Accepted: 04/07/2025] [Indexed: 05/15/2025]
Abstract
INTRODUCTION Physical inactivity contributes to non-communicable disease (NCD) health burden, making it essential to study and address this issue at a population level. The present research aims to explore the patterns of physical activity (PA) in Haryana through a subgroup analysis of the national Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study. METHODS This study was conducted between December 2018 and July 2019 in Haryana and included 3918 adult participants. Physical activity was assessed using the validated MDRF Physical Activity Questionnaire (MPAQ), which has domain-wise assessments of PA. Weighted prevalence was estimated using state-specific sampling weights, and associations between PA, anthropometric and biochemical profiles were assessed using bivariate analysis done using Student's unpaired t tests, one-way analysis of variance (ANOVA), or chi-square tests. Factors describing the likelihood of being active were ascertained using a multivariable nominal regression analysis. RESULTS About 73% of the study participants were physically inactive, and only 27% were moderately to vigorously active. The time spent in different PA domains varied significantly across sociodemographic variables, including sex, education, region, occupation, and socioeconomic status. Participants from the middle socioeconomic class spent more time in work-related PA, compared to low and upper-class participants who spent more time in general and transport-related PA. There were significant statistical differences between active and non-active groups concerning their mean blood glucose levels, body mass index, waist circumference and systolic blood pressure, but the differences in the lipid profile were non-significant. However, regression analysis showed higher odds of being physically active among younger participants, men, residents in rural areas, and those having fewer years of education. CONCLUSION We highlight the alarmingly high prevalence of physical inactivity across different segments of society in Haryana with significant sociodemographic disparities. Considering the increasing prevalence of NCDs, it is high time to prioritise health promotion measures and inculcate more physical activity amongst the population to achieve health-related sustainable development goals.
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Affiliation(s)
- Madhur Verma
- Department of Community and Family Medicine, All India Institute of Medical Sciences Bathinda, Bathinda, India
| | - Sanjay Kalra
- Department of Endocrinology, Bharti Hospital, Karnal, India.
- University Centre for Research and Development, Chandigarh University, Mohali, India.
| | - Mohan Deepa
- Department of Epidemiology, Madras Diabetes Research Foundation, Chennai, India
| | | | - Nikita Sharma
- Department of Community and Family Medicine, All India Institute of Medical Sciences Bilaspur, Bilaspur, India
| | - Rajendra Pradeepa
- Department of Research Operations and Diabetes Complications, Madras Diabetes Research Foundation, Chennai, India
| | - Kirti Chauhan
- Indian Institute of Public Health, Shillong (IIPHs), Meghalaya, India
| | - Omna Singh
- Department of Community and Family Medicine, All India Institute of Medical Sciences Bathinda, Bathinda, India
| | - Nirmal Elangovan
- Department of Research Operations and Diabetes Complications, Madras Diabetes Research Foundation, Chennai, India
| | | | - Rakesh Kakkar
- Department of Community and Family Medicine, All India Institute of Medical Sciences Bathinda, Bathinda, India
| | - R S Dhaliwal
- Division of Non-Communicable Diseases, Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Ansari Nagar, New Delhi, 110029, India
| | - Tanvir Kaur
- Division of Non-Communicable Diseases, Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Ansari Nagar, New Delhi, 110029, India
| | - Viswanathan Mohan
- Madras Diabetes Research Foundation, Dr. Mohan's Diabetes Specialties Centre, Chennai, India
| | - Ranjit Mohan Anjana
- Madras Diabetes Research Foundation, Dr. Mohan's Diabetes Specialties Centre, Chennai, India
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11
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Barragan-Zuñiga J, Herrera MD, Simental-Mendía LE, Zamilpa A, Morales-Ferra DL, Martínez-Aguilar G, Salas-Pacheco J, Gamboa-Gómez CI. A Combined Turmeric and Allspice Supplement Improves Metabolic Health in Obese Rats by Reducing Carbohydrate and Lipid Absorption. J Med Food 2025. [PMID: 40358049 DOI: 10.1089/jmf.2024.0024] [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: 05/15/2025] Open
Abstract
The objective of this study is to assess the impact of a combined turmeric (Curcuma longa L.) and allspice (Pimenta dioica L. Merril) supplement (TAS), on obesity, hypertriglyceridemia, hyperglycemia, and insulin resistance through inhibition of carbohydrate and lipid absorption. In vitro assessments demonstrated that TAS inhibits key enzymes implicated in the carbohydrate and lipid absorption. Oral starch and lipid tolerance tests showed that combined supplement reduced lipid (∼47% TAS) and carbohydrate absorption (∼33%) compared to the negative control. In a 36-week diet-induced obesity model, intervention with TAS was found that reduced body weight gain (∼18%), lower triglycerides (∼35%), and fasting glucose levels (∼14%) compared to obese control. Furthermore, TAS-treated rats showed reduced oral glucose tolerance test values (∼25%), insulin levels (∼14%), and insulin resistance (∼14%). Our results suggest that TAS enhances carbohydrate and lipid absorption while effectively improving hypertriglyceridemia, hyperglycemia, and insulin resistance in obese rats.
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Affiliation(s)
| | - Mayra Denise Herrera
- Instituto Nacional de Investigaciones Forestales Agrícolas y Pecuarias, Campo Experimental Zacatecas, Zacatecas-Fresnillo, Mexico
| | - Luis E Simental-Mendía
- Unidad de Investigación Biomédica del Instituto Mexicano del Seguro Social, Durango, México
| | - Alejandro Zamilpa
- Centro de Investigación Biomédica del Sur, Instituto Mexicano del Seguro Social, Morelos, México
| | | | | | - José Salas-Pacheco
- Instituto de Investigación Científica, Universidad Juárez del Estado de Durango, Durango, México
| | - Claudia I Gamboa-Gómez
- Unidad de Investigación Biomédica del Instituto Mexicano del Seguro Social, Durango, México
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12
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Zhang Y, Bai C, Sha J, Huo X, Qu D, Chen J. Ginseng Soluble Dietary Fiber Reverses Obesity via the PPAR/AMPK Signaling Pathway and Improves Intestinal Flora in Mice. Foods 2025; 14:1716. [PMID: 40428495 DOI: 10.3390/foods14101716] [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: 04/07/2025] [Revised: 05/04/2025] [Accepted: 05/08/2025] [Indexed: 05/29/2025] Open
Abstract
BACKGROUND Ginseng soluble dietary fiber (GSDF) has been shown to have good physicochemical properties; however, its in vivo benefits in obesity are yet to be fully elucidated. METHODS To explore this, C57BL/6J obese mice were given metformin hydrochloride and different doses of GSDF for 60 days. The levels of blood lipids and inflammatory factors were detected by ELISA, and the pathological alterations were detected through the application of HE staining. The level of adipose tissue protein in epididymis was detected by Western blotting and through the effects of 16S rRNA sequencing on gut microbiota. RESULTS The results showed that GSDF significantly improved basal physiological indices, lipid levels, and serum cytokine levels in the obese mice. GSDF increased the expression levels of PPAR-γ, AMPK, and P-AMPK proteins, and lowered the expression of IL-1β, TNF-α, and other proteins in the adipose tissues of the epididymis, in turn inhibiting adipogenesis and ameliorating lipid metabolism disorders. By lowering the Firmicutes/Bacteroidetes ratio in the gut and altering the abundance of thick-walled bacteria and mycobacterium, the abundance of species such as Lactobacillus, Alloprevotella, and Faecalibaculum was altered to improve cecum health. CONCLUSIONS These results suggest that GSDF may have a positive effect on growth, obesity, and cecal health in obese mice.
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Affiliation(s)
- Yue Zhang
- Institute of Special Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China
| | - Chen Bai
- Institute of Special Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China
| | - Jiyue Sha
- Institute of Special Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China
| | - Xiaohui Huo
- Institute of Special Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China
| | - Di Qu
- Institute of Special Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China
| | - Jianbo Chen
- Institute of Special Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China
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Nemoto S, Uchida K, Kubota T, Nakayama M, Han YW, Koyasu S, Ohno H. Tetraspanin7 in adipose tissue remodeling and its impact on metabolic health. Mol Metab 2025; 97:102168. [PMID: 40368161 DOI: 10.1016/j.molmet.2025.102168] [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: 04/10/2025] [Revised: 05/07/2025] [Accepted: 05/08/2025] [Indexed: 05/16/2025] Open
Abstract
OBJECTIVE We previously identified tetraspanin 7 (Tspan7) as a candidate gene influencing body weight in an obesity-related gene screening study. However, the mechanisms underlying its involvement in body weight regulation remained unclear. This study aims to investigate the role of TSPAN7 from a metabolic perspective. METHODS We utilized genetically modified mice, including adipose tissue-specific Tspan7-knockout and Tspan7-overexpressing models, as well as human adipose-derived stem cells with TSPAN7 knockdown and overexpression. Morphological, molecular, and omics analyses, including proteomics and transcriptomics, were performed to investigate TSPAN7 function. Physiological effects were assessed by measuring blood markers associated with lipid regulation under metabolic challenges, such as high-fat feeding and aging. RESULTS We show that TSPAN7 is involved in regulating lipid droplet formation and stabilization. Tspan7-knockout mice exhibited an increased proportion of small-sized adipocytes and a reduced visceral-to-subcutaneous fat ratio. This shift in fat distribution was associated with improved insulin sensitivity and altered branched-chain amino acid metabolism, as evidenced by increased expression of the branched-chain α-keto acid dehydrogenase complex subunit B in Tspan7-modified mice. Mechanistically, TSPAN7 deficiency promoted subcutaneous fat expansion, alleviating metabolic stress on visceral fat, a major contributor to insulin resistance. CONCLUSIONS TSPAN7 influences lipid metabolism by modulating adipose tissue remodeling, particularly under metabolic challenges, such as high-fat diet exposure and aging. Its modulation enhances subcutaneous fat storage capacity while mitigating visceral fat accumulation, leading to improved insulin sensitivity. These findings position TSPAN7 as a potential target for therapeutic interventions aimed at improving metabolic health and preventing obesity-related diseases.
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Affiliation(s)
- Shino Nemoto
- Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
| | - Kazuyo Uchida
- Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
| | - Tetsuya Kubota
- Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Tokyo, Japan; Division of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, Japan; Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Manabu Nakayama
- Laboratory of Medical Omics Research, Department of Frontier Research and Development, Kazusa DNA Research Institute, Kisarazu, Chiba, Japan
| | - Yong-Woon Han
- Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
| | - Shigeo Koyasu
- Laboratory for Immune Cell Systems, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
| | - Hiroshi Ohno
- Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Laboratory for Immune Regulation, Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Chiba, Chiba, Japan
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Street ME, Casadei F, Di Bari ER, Ferraboschi F, Montani AG, Shulhai AM, Esposito S. The Role of Nutraceuticals and Probiotics in Addition to Lifestyle Intervention in the Management of Childhood Obesity-Part 1: Metabolic Changes. Nutrients 2025; 17:1630. [PMID: 40431370 DOI: 10.3390/nu17101630] [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: 04/04/2025] [Revised: 05/01/2025] [Accepted: 05/07/2025] [Indexed: 05/29/2025] Open
Abstract
Childhood obesity is a growing global health issue. Its rising prevalence is linked to genetic, environmental, and lifestyle factors. Obesity in children could lead to different comorbidities and complications with an increased risk of metabolic disorders, such as insulin resistance, dyslipidemia, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD). First-line treatment involves dietary modifications and lifestyle changes; however, adherence is often poor and remains a significant challenge. Pharmacotherapy, while a potential option, has limitations in availability and can cause side effects, leading to growing interest in alternative treatments, such as nutraceutical compounds. Derived from natural sources, these compounds have different anti-inflammatory, antiallergic, antioxidant, antibacterial, antifungal, neuroprotective, antiaging, antitumor, insulin-sensitizing, glucose, and lipid-lowering effects. This review describes commonly used nutraceutical compounds, such as omega-3 fatty acids, vitamin D, polyphenols (such as resveratrol and curcumin), berberine, white mulberry leaves and others, and pre- and probiotics in the management of obesity, evaluating the evidence on their mechanisms of action and efficacy in metabolic comorbidities. The evidence suggests that the integration of nutraceuticals into the diet may positively influence body mass index, glucose metabolism, lipid profiles, and gut microbiota composition and reduce inflammation in obese individuals. These effects may provide future practical guidance for clinical practice, contribute to metabolic health improvement, and potentially prevent obesity-related complications. In this first part, we discuss the effects of nutraceutical compounds on insulin sensitivity and insulin resistance, T2DM, dyslipidemia, and MASLD in addition to diet and lifestyle interventions.
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Affiliation(s)
- Maria Elisabeth Street
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
- Unit of Paediatrics, P. Barilla Children's Hospital, University Hospital of Parma, 43126 Parma, Italy
| | - Federica Casadei
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Erika Rita Di Bari
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | | | | | | | - Susanna Esposito
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
- Unit of Paediatrics, P. Barilla Children's Hospital, University Hospital of Parma, 43126 Parma, Italy
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15
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Xu H, Xie J, Niu H, Cai X, He P. Associations between triglyceride-glucose body mass index and all-cause mortality in ICU patients with sepsis and acute heart failure. BMC Cardiovasc Disord 2025; 25:359. [PMID: 40346499 PMCID: PMC12063255 DOI: 10.1186/s12872-025-04804-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Accepted: 04/28/2025] [Indexed: 05/11/2025] Open
Abstract
BACKGROUND The triglyceride‒glucose body mass index (TyG-BMI) has been recognized as a significant predictor of cardiovascular disease risk and plays a crucial role in assessing insulin resistance. However, the correlation between the TyG-BMI and clinical outcomes in patients with sepsis and acute heart failure (AHF) has not been sufficiently explored. This study aimed to investigate the associations between TyG-BMI and clinical outcomes in patients with sepsis and AHF. METHODS We conducted a retrospective analysis of ICU-admitted patients via data from the MIMIC-IV database. Multivariable logistic regression, sensitivity analysis, and restricted cubic spline (RCS) models were used to assess the relationship between TyG-BMI and all-cause mortality. K‒M survival analysis and Boruta analysis were employed to evaluate the predictive value of the TyG-BMI. Subgroup analyses considered the effects of age, sex, ethnicity, and comorbidities. RESULTS Among the 1,729 patients, a higher TyG-BMI was associated with lower all-cause mortality at 90 and 180 days. Each standard deviation increase in the TyG-BMI was linked to 0.2% and 0.3% reductions in 90-day and 180-day all-cause mortality, respectively. Kaplan‒Meier analysis revealed significantly lower all-cause mortality in patients with higher TyG-BMIs (P < 0.0001). The RCS model revealed a nonlinear relationship between the TyG-BMI and mortality. Boruta analysis identified the TyG-BMI as an important clinical feature. Sensitivity analyses revealed that the association remained significant after patients with myocardial infarction, malignancies, or missing data were excluded. The subgroup analysis revealed that for the 90-day and 180-day mortality rates, significant interactions were found only in the subgroup of patients with kidney diseases (P < 0.05). CONCLUSION The TyG-BMI may have potential value in predicting mortality in ICU patients with sepsis and AHF, supporting early risk assessment and clinical intervention. This study provides critical insights into patient prognosis.
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Affiliation(s)
- Heping Xu
- Department of Emergency Medicine, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou City, Hainan Province, 570311, China.
| | - Jinyuan Xie
- Department of Emergency Medicine, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou City, Hainan Province, 570311, China
| | - Huan Niu
- Department of Emergency Medicine, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou City, Hainan Province, 570311, China
| | - Xiongwei Cai
- Department of Emergency Medicine, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou City, Hainan Province, 570311, China
| | - Ping He
- Department of Emergency Medicine, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou City, Hainan Province, 570311, China
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Chen LL, Tohit NM, Ludin AFM, Manaf ZA, Wong A, Kuan KL, Chien HW, Shahar S. Efficacy of diabetes-specific partial meal replacement on glycemic and weight control in type 2 diabetes: A randomized controlled trial. Diabetes Obes Metab 2025. [PMID: 40345156 DOI: 10.1111/dom.16446] [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: 11/26/2024] [Revised: 04/18/2025] [Accepted: 04/26/2025] [Indexed: 05/11/2025]
Abstract
AIMS To evaluate the efficacy of a diabetes-specific formula (DSF)-based partial meal replacement (PMR) in improving glycemic control, weight, and underlying hormonal changes among participants with type 2 diabetes and overweight or obesity compared to dietary consultation. MATERIALS AND METHODS This 12-week, parallel randomized controlled trial was conducted at Hospital Canselor Tuanku Muhriz, National University of Malaysia, from February 2022 to March 2024. Adults aged 20-65 years with type 2 diabetes [haemoglobin A1c (HbA1c) ≥7.5%] and overweight or obesity were randomized into two groups: PMR with DSF (Metabolic+ Sauver) plus dietary consultation (treatment group) or dietary consultation alone (control group). The primary endpoint was mean change in HbA1c at week 12. RESULTS Among 156 participants (mean age 52.2 ± 9.7 years), 141 completed the 12-week intervention. The treatment group had a greater HbA1c reduction compared to controls (-0.83% vs. -0.19%; MD: -0.63%; 95% CI: -1.00, -0.27; p < 0.001). A significantly higher proportion of the treatment group participants (61.4%) achieved clinically significant HbA1c reduction (≥0.5%) compared to controls (42.3%, p = 0.023). Fasting glucose, insulin, and anthropometric measurements also significantly improved in the treatment group compared to controls. Subsample analysis on hormonal changes revealed significant improvements in adiponectin levels among the treatment group. CONCLUSION This study demonstrated that PMR with DSF significantly improved glycemic and weight management in participants with type 2 diabetes and overweight or obesity. Adiponectin levels increased in the treatment group, correlating with improved glycemic control. No adverse events were observed on liver and kidney profiles, highlighting its potential as a safe and effective approach for diabetes management.
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Affiliation(s)
- Lew Leong Chen
- Center for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
- Biomedical Science Programme, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Noorlaili Mohd Tohit
- Department of Family Medicine, Faculty of Medicine, University Kebangsaan Malaysia Medical Centre (UKMMC), Kuala Lumpur, Malaysia
| | - Arimi Fitri Mat Ludin
- Center for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
- Biomedical Science Programme, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Zahara Abdul Manaf
- Center for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
- Dietetic Programme, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Alicia Wong
- Alpro Academy, Alpro Group, Sendayan Techvalley, Seremban, Malaysia
| | - Kwan Lee Kuan
- Alpro Academy, Alpro Group, Sendayan Techvalley, Seremban, Malaysia
| | - Han Wan Chien
- Alpro Academy, Alpro Group, Sendayan Techvalley, Seremban, Malaysia
| | - Suzana Shahar
- Center for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
- Dietetic Programme, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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17
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Sun C, Wen X, Chu X, Yuan F, Chen Y, Peng C, Qian M, Mei J, Wang J, Jiang Y, Xu S, Wang C, Li W, Zhang J. Adipocyte exosome miR-4472 inhibits glucose uptake in skeletal muscle through downregulation of MEF2D. J Diabetes Investig 2025. [PMID: 40342203 DOI: 10.1111/jdi.70054] [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: 10/26/2024] [Revised: 04/11/2025] [Accepted: 04/16/2025] [Indexed: 05/11/2025] Open
Abstract
AIMS/INTRODUCTION Previous studies have found that miR-4472 is overexpressed in the serum of individuals with obesity and type 2 diabetes mellitus (T2DM), which may participate in the process of obesity-induced T2DM. However, a role for miR-4472 in the process has not been demonstrated. Here, we aim to investigate whether the increased content of miR-4472 in adipose tissue derived from exosomes inhibits glucose uptake in skeletal muscle by downregulating the expression of its target gene. MATERIALS AND METHODS In vitro C2C12 and 3T3-L1 cells, and in vivo diet-induced obesity mouse models and AT-Dicer KO mice were used to assess the impact of miR-4472 on glucose uptake and insulin sensitivity. We also evaluated the effects of serum exosomes from normal and obese individuals on insulin sensitivity in mice and the expression of miR-4472 and target genes in skeletal muscle. RESULTS miR-4472 exhibits a strong positive correlation with BMI, waist circumference, hip circumference, and FPG. The content of miR-4472 derived from adipose tissue exosomes increases in the circulation in a state of obesity, which can induce insulin resistance by targeting the expression of MEF2D/GLUT4, inhibiting the glucose consumption and uptake ability of skeletal muscle cells. Both exosome inhibitors and miR-4472 inhibitors can reverse the inhibitory effect of miR-4472 on MEF2D/GLUT4 expression and glucose intake and uptake ability. Additionally, they can improve insulin resistance caused by increased miR-4472 levels in mice with obesity. CONCLUSIONS Adipocyte exosome miR-4472 inhibits glucose uptake in skeletal muscle through downregulating the expression of MEF2D/GLUT4.
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Affiliation(s)
- Chaoyue Sun
- Ministry of Education Key Laboratory of Xinjiang Endemic and Ethnic Disease, Shihezi, Xinjiang, China
| | - Xin Wen
- Medical College of Shihezi University, Shihezi, Xinjiang, China
| | - Xiaolong Chu
- Medical College of Shihezi University, Shihezi, Xinjiang, China
- Medical College of Tarim University, Alaer, Xinjiang, China
| | - Fangyuan Yuan
- Medical College of Shihezi University, Shihezi, Xinjiang, China
| | - Yao Chen
- Medical College of Shihezi University, Shihezi, Xinjiang, China
| | - Chaoling Peng
- Medical College of Shihezi University, Shihezi, Xinjiang, China
| | - Meiyu Qian
- Medical College of Shihezi University, Shihezi, Xinjiang, China
| | - Jin Mei
- Medical College of Shihezi University, Shihezi, Xinjiang, China
| | - Juan Wang
- Medical College of Shihezi University, Shihezi, Xinjiang, China
| | - Yidan Jiang
- Medical College of Shihezi University, Shihezi, Xinjiang, China
| | - Shibo Xu
- Medical College of Shihezi University, Shihezi, Xinjiang, China
| | - Cuizhe Wang
- Medical College of Shihezi University, Shihezi, Xinjiang, China
| | - Wei Li
- Medical College of Shihezi University, Shihezi, Xinjiang, China
- The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, China
| | - Jun Zhang
- Ministry of Education Key Laboratory of Xinjiang Endemic and Ethnic Disease, Shihezi, Xinjiang, China
- Medical College of Shihezi University, Shihezi, Xinjiang, China
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Ratwani M, Bisht S, Prakash S. Association between sleep disturbance and metabolic dysfunctions in adipose tissue: Insights into melatonin's role. Biochem Biophys Res Commun 2025; 770:151978. [PMID: 40378618 DOI: 10.1016/j.bbrc.2025.151978] [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: 01/23/2025] [Revised: 05/08/2025] [Accepted: 05/08/2025] [Indexed: 05/19/2025]
Abstract
The increased prevalence of sleep disturbances in modern society is frequently linked to various metabolic disorders, including insulin resistance, obesity, hypertension, fatty liver disease, and cardiometabolic complications. Melatonin, a pineal gland-secreted neurohormone, plays a pivotal role in maintaining the circadian rhythm. It is involved in regulating adipose tissue development, lipid accumulation, browning of white adipose tissue, and activation of brown adipose tissue. The adipose tissue is a dynamic endocrine organ that secretes hormones and cytokines. Recent research has highlighted the significant role of melatonin in the modulation of lipid metabolism, adipogenesis, and thermogenesis in adipose tissues. Circadian rhythms are important in synchronizing metabolic functions with environmental cues, such as light and dark, feeding-fasting states, etc. Irregular sleep patterns, shift work, and exposure to artificial light at night disrupt these rhythms, affecting circadian regulation and compromising metabolic health. Melatonin imbalance due to sleep disturbances results in metabolic dysfunction, increased fat storage, and adipose tissue inflammation. As circadian rhythm and melatonin are both related, a change in circadian rhythm affects the physiology of adipose tissues thereby precipitating metabolic complications through melatonin signaling. This study attempted to understand the mechanisms by which melatonin influences adipose tissue activity, highlighting the role of circadian rhythms in this process. This will enable the development of melatonin-based therapies to mitigate the adverse effects of chronobiological disturbances on the physiology of adipose tissue. Understanding these interactions will provide novel insights for combating obesity and related metabolic conditions.
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Affiliation(s)
- Mishthi Ratwani
- Amity Institute of Pharmacy, Amity University, Sector 125, Uttar Pradesh, Lucknow, 201313, India
| | - Shradha Bisht
- College of Pharmacy, Shivalik Campus, Dehradun, 248197, Uttarakhand, India
| | - Swati Prakash
- Amity Institute of Pharmacy, Amity University, Sector 125, Uttar Pradesh, Lucknow, 201313, India.
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19
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Gu Q, Wang L, Xu M, Zhou W, Liu G, Tian H, Efferth T, Wang C, Fu Y. The natural dihydrochalcone phloretin reduces lipid accumulation via downregulation of IIS and sbp-1/ SREBP pathways in HepG2 cells and Caenorhabditis elegans. Food Funct 2025. [PMID: 40326995 DOI: 10.1039/d5fo01105a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Abstract
Phloretin, a natural dihydrochalcone, exhibits significant potential in modulating lipid metabolism both in vitro and in vivo. This study investigated the effects of phloretin on lipid accumulation in HepG2 cells and Caenorhabditis elegans. In HepG2 cells, phloretin reduced lipid accumulation, ROS levels, and lipid peroxidation while ameliorating mitochondrial dysfunction. It downregulated lipid synthesis genes (SREBP, FASN) and upregulated PI3K-AKT pathway genes (AKT, FOXO, MTOR). In C. elegans, phloretin alleviated lipid accumulation-induced growth and locomotor impairments, reduced lipofuscin, ROS, glucose, and triglyceride levels, and modulated amino acid and lipid metabolism pathways. Gene expression analysis revealed downregulation of sbp-1, mdt-15, fat-5, fat-6, and fat-7, and upregulation of daf-16, age-1, and skn-1. Mutant studies confirmed that phloretin's lipid-lowering effects were mediated through the IIS and sbp-1/SREBP pathways. These findings suggest phloretin is a promising candidate for regulating lipid metabolism and preventing hyperlipidemia.
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Affiliation(s)
- Qi Gu
- The College of Forestry, Beijing Forestry University, 100083, Beijing, PR China.
| | - Litao Wang
- The College of Forestry, Beijing Forestry University, 100083, Beijing, PR China.
| | - Mingyue Xu
- The College of Forestry, Beijing Forestry University, 100083, Beijing, PR China.
| | - Wanmei Zhou
- The College of Forestry, Beijing Forestry University, 100083, Beijing, PR China.
| | - Guosheng Liu
- The College of Forestry, Beijing Forestry University, 100083, Beijing, PR China.
| | - Haiting Tian
- The College of Forestry, Beijing Forestry University, 100083, Beijing, PR China.
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | - Chenlu Wang
- The College of Forestry, Beijing Forestry University, 100083, Beijing, PR China.
| | - Yujie Fu
- The College of Forestry, Beijing Forestry University, 100083, Beijing, PR China.
- Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, 150040, Harbin, PR China
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20
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Nie P, Hu L, Feng X, Xu H. Gut Microbiota Disorders and Metabolic Syndrome: Tales of a Crosstalk Process. Nutr Rev 2025; 83:908-924. [PMID: 39504479 DOI: 10.1093/nutrit/nuae157] [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] [Indexed: 11/08/2024] Open
Abstract
The microbiota in humans consists of trillions of microorganisms that are involved in the regulation of the gastrointestinal tract and immune and metabolic homeostasis. The gut microbiota (GM) has a prominent impact on the pathogenesis of metabolic syndrome (MetS). This process is reciprocal, constituting a crosstalk process between the GM and MetS. In this review, GM directly or indirectly inducing MetS via the host-microbial metabolic axis has been systematically reviewed. Additionally, the specifically altered GM in MetS are detailed in this review. Moreover, short-chain fatty acids (SCFAs), as unique gut microbial metabolites, have a remarkable effect on MetS, and the role of SCFAs in MetS-related diseases is highlighted to supplement the gaps in this area. Finally, the existing therapeutics are outlined, and the superiority and shortcomings of different therapeutic approaches are discussed, in hopes that this review can contribute to the development of potential treatment strategies.
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Affiliation(s)
- Penghui Nie
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Liehai Hu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Xiaoyan Feng
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Hengyi Xu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
- International Institute of Food Innovation Co., Ltd, Nanchang University, Nanchang 330200, China
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21
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Wang H, He M, Bat-Erdene B, Li Y, Ta D. Low-intensity Pulsed Ultrasound Stimulation of the Intestine Improves Insulin Resistance in Type 2 Diabetes. ULTRASOUND IN MEDICINE & BIOLOGY 2025; 51:797-806. [PMID: 39915223 DOI: 10.1016/j.ultrasmedbio.2025.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 01/08/2025] [Accepted: 01/09/2025] [Indexed: 03/19/2025]
Abstract
OBJECTIVE Ultrasound stimulation of internal organs and peripheral nerves has demonstrated promising potential in regulating blood glucose metabolism. This study aims to assess the effectiveness of low-intensity pulsed ultrasound stimulation (LIPUS) on intestine in improving insulin resistance with type 2 diabetes mellitus (T2DM). METHODS C57BL/6J mice, both normal and T2DM, were randomly divided into three groups: Control, T2D-sham, and T2D-LIPUS. The T2D-LIPUS group received LIPUS stimulation in the intestine. The parameters were as follows: 1 MHz frequency, 1.0 kHz pulse repetition frequency (PRF), 20% duty cycle, 100 mW/cm² intensity spatial average temporal average (ISATA), for 20 minutes per session, five days per week, over four weeks. RESULTS Blood glucose analysis indicated that mice in the T2D-LIPUS group displayed significantly lower area under the curve (AUC) of glucose tolerance tests (GTT) and insulin tolerance tests (ITT) (p < 0.001), HOMA-IR (p < 0.001), and fasting serum insulin levels (p < 0.01) compared to the T2D-sham group. LIPUS treatment effectively lowered serum levels of IL-1β (p < 0.001) and TNF-α (p < 0.01) along with mRNA expression levels of IL-1β (p < 0.01) and IL-18 (p < 0.001) in the intestines of T2DM mice. Additionally, Western blot analysis revealed a reduction in the protein levels of NLRP3, caspase-1, and GSDMD-N in the intestinal tissues of mice treated with LIPUS. CONCLUSION These findings suggest that LIPUS can reduce inflammation and cellular apoptosis, while improving insulin resistance by inhibiting the NLRP3/Caspase-1/GSDMD signaling pathway. This research introduces a novel, non-pharmacological approach for managing T2DM.
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Affiliation(s)
- Huan Wang
- Department of Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, China
| | - Min He
- Department of Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, China
| | - Badamgarav Bat-Erdene
- Department of Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, China
| | - Ying Li
- Department of Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, China.
| | - Dean Ta
- Department of Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, China
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22
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Sleiman L, Dinescu S. Role of Non-Coding RNAs in White and Brown Adipose Tissue Differentiation and Development. Noncoding RNA 2025; 11:30. [PMID: 40407588 PMCID: PMC12101253 DOI: 10.3390/ncrna11030030] [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: 02/28/2025] [Revised: 04/18/2025] [Accepted: 04/28/2025] [Indexed: 05/26/2025] Open
Abstract
Adipocyte differentiation is a complex process in which pluripotent mesenchymal stem cells (MSCs) differentiate and develop into mature fat cells, also known as adipocytes. This process is controlled by various transcription factors, hormones, and signaling molecules that regulate the development of these cells. Recently, an increasing number of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), have been established to be involved in the regulation of many biological processes, including adipocyte differentiation, development, metabolism, and energy homeostasis of white and brown adipose tissue. Several in vitro and in vivo studies reported the significant role of ncRNAs in either promoting or inhibiting adipocyte differentiation into white or brown fat cells by targeting specific transcription factors and regulating the expression of key adipogenic genes. Identifying the function of ncRNAs and their subsequent targets contributes to our understanding of how these molecules can be used as potential biomarkers and tools for therapies against obesity, diabetes, and other diseases related to obesity. This could also contribute to advancements in tissue-engineering based treatments. In this review, we intended to present an up-to-date comprehensive literature overview of the role of ncRNAs, including miRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), focusing particularly on miRNAs, in regulating the differentiation and development of cells into white and brown adipose tissue. In addition, we further discuss the potential use of these molecules as biomarkers for the development of novel therapeutic strategies for future personalized treatment options for patients.
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Affiliation(s)
- Lea Sleiman
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania;
| | - Sorina Dinescu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania;
- Research Institute of the University of Bucharest (ICUB), 050663 Bucharest, Romania
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23
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Que Z, Chen D, Cai H, Lan W, Huang Y, Rui G. Associations between insulin resistance and low back pain risk in US adults: a cross-sectional study. Front Med (Lausanne) 2025; 12:1538754. [PMID: 40357296 PMCID: PMC12066540 DOI: 10.3389/fmed.2025.1538754] [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: 12/03/2024] [Accepted: 04/09/2025] [Indexed: 05/15/2025] Open
Abstract
Background Insulin resistance is one of the major pathophysiological features of type 2 diabetes mellitus. Studies have revealed the association between type 2 diabetes mellitus and low back pain. However, few studies explored the relationship between insulin resistance and low back pain directly. Therefore, this study selected HOMA-IR, TyG, TyG-BMI, TyG-WC, and TyG-WtHR as indicators of insulin resistance to comprehensively investigate the association between insulin resistance and low back pain. Methods The data for this cross-sectional study were from NHANES. Multivariate logistic regression was used to assess the association of insulin resistance with low back pain, and the stability of the results was evaluated by stratified analysis. Results A total of 6,126 adult participants were included in the study, including 3,657 non-LBP participants and 2,469 LBP patients. All of these five indices showed significant association with low back pain after full adjustment for all covariates (Model 3), HOMA-IR [OR = 1.052, 95% CI (1.018, 1.087), p = 0.003], TyG [OR = 1.431, 95% CI (1.013, 2.021), p = 0.042], TyG-BMI [OR = 1.003, 95% CI (1.002, 1.005), p < 0.0001], TyG-WC [OR = 1.001, 95% CI (1.001, 1.002), p < 0.0001], TyG-WtHR [OR = 1.268, 95% CI (1.155, 1.393), p < 0.0001]. The relationship between insulin resistance and low back pain is stable in most stratified populations (p-interaction >0.05). Conclusion Insulin resistance is associated with an increased risk of low back pain. The HOMA-IR, TyG, TyG-WC, TyG-BMI, and TyG-WtHR all showed a stable correlation with low back pain. TyG-BMI, TyG-WC, and TyG-WtHR are more stable in their associations with low back pain than TyG alone.
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Affiliation(s)
- Zhiqiang Que
- Department of Orthopedics, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Dingqiang Chen
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, China
| | - Huirong Cai
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, China
- Department of Orthopedics, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Weibin Lan
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, China
- Department of Orthopedics, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Yuxuan Huang
- Xiamen Key Laboratory of Clinical Efficacy and Evidence Studies of Traditional Chinese Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Gang Rui
- Department of Orthopedics, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, China
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24
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Lin WS, Lin YL, Koh YC, Ho PY, Lin YC, Ho CT, Pan MH. 5-Demethyl-Polymethoxyflavones Mitigate Obesity by Reducing Adipose Tissue Inflammation, Promoting Browning, and Modulating Gut Microbiota in High-Fat Diet-Fed Mice. Mol Nutr Food Res 2025:e70069. [PMID: 40277157 DOI: 10.1002/mnfr.70069] [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: 01/07/2025] [Revised: 02/24/2025] [Accepted: 04/03/2025] [Indexed: 04/26/2025]
Abstract
Given the escalating prevalence of obesity worldwide, identifying efficacious dietary components is crucial. This study investigated whether citrus-derived 5-demethyl-polymethoxyflavones (5-DPMFs) protect against obesity in high-fat diet (HFD)-induced obese mice. Male C57BL/6 mice were fed an HFD and supplemented with a citrus-derived powder (CP) containing 5-DPMFs as the main bioactive components. Two doses of CP (0.25% and 1% in the diet) were tested, corresponding to approximately 36 and 145 mg/kg body weight of 5-DPMFs, respectively. Key adipose tissue parameters were assessed, including inflammatory cytokines and browning markers associated with p38 MAPK signaling. Treatment with 5-DPMFs significantly attenuated adipose tissue inflammation, as evidenced by reduced levels of MCP-1, TNF-α, IL-6, and IL-1β. Concurrently, fat browning was enhanced by upregulating thermogenic and mitochondrial proteins. Gut microbiota analysis revealed that 5-DPMFs increased the relative abundance of beneficial probiotic species, such as Lactobacillus and Limosilactobacillus reuteri, which have been linked to improved metabolic profiles. These findings demonstrate that 5-DPMFs mitigate obesity-associated adipose inflammation, promote the browning of white adipose tissue (WAT), and favorably regulate gut microbiota composition in HFD-fed mice. Our results suggest that 5-DPMFs could serve as a functional food ingredient for obesity prevention and management.
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Affiliation(s)
- Wei-Sheng Lin
- Department of Food Science, National Quemoy University, Kinmen, Taiwan
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
| | - Yu-Lu Lin
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
| | - Yen-Chun Koh
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
| | - Pin-Yu Ho
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
| | - Yu-Cheng Lin
- Greenyn Biotechnology Co Ltd Taichung City, Taichung City, Taiwan
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, New Jersey, USA
| | - Min-Hsiung Pan
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung City, Taiwan
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25
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Dhurandhar Y, Tomar S, Das A, Prajapati JL, Singh AP, Bodake SH, Namdeo KP. Chronic inflammation in obesity and neurodegenerative diseases: exploring the link in disease onset and progression. Mol Biol Rep 2025; 52:424. [PMID: 40274681 DOI: 10.1007/s11033-025-10509-z] [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: 03/07/2025] [Accepted: 04/14/2025] [Indexed: 04/26/2025]
Abstract
Obesity, a worldwide health emergency, is defined by excessive fat accumulation and significantly impacts metabolic health. In addition to its recognized association with cardiovascular disease, diabetes, and other metabolic illnesses, recent studies have revealed the connection between obesity and neurodegeneration. The main reason for this link is inflammation caused by the growth of fat tissue, which activates harmful processes that affect how the brain works. Fat tissue, particularly the fat around the organs, produces various substances that cause inflammation, such as cytokines (TNF-α, IL-6), adipokines (leptin, resistin), and free fatty acids. These chemicals cause low-grade, persistent systemic inflammation, which is becoming more widely acknowledged as a major factor in peripheral metabolic dysfunction and pathology of the central nervous system (CNS). Inflammatory signals in the brain cause neuroinflammatory reactions that harm neuronal structures, change neuroplasticity, and disrupt synaptic function. When obesity-related inflammation is present, the brain's resident immune cells, known as microglia, become hyperactivated, which can lead to the production of neurotoxic chemicals, which can cause neuronal death. This neuroinflammation exacerbates the negative effects of obesity on brain health and is linked to cognitive decline, Alzheimer's disease, and other neurodegenerative disorders. Moreover, the blood-brain barrier (BBB) exhibits increased permeability during inflammatory states, facilitating the infiltration of peripheral immune cells and cytokines into the brain, hence exacerbating neurodegeneration. Adipose tissue is a source of chronic inflammatory mediators, which are examined in this review along with the molecular pathways that connect inflammation brought on by obesity to neurodegeneration. Additionally, it addresses various anti-inflammatory treatment approaches, including lifestyle modifications, anti-inflammatory medications, and gut microbiota modulation, to lessen the metabolic and neurological effects of obesity. Recognizing the link between obesity and inflammation opens up new opportunities for early intervention and the development of targeted treatments to prevent or alleviate neurodegenerative disorders.
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Affiliation(s)
- Yogita Dhurandhar
- Department of Pharmacy, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh, 495009, India
| | - Shubham Tomar
- Pharmacovigilance Programme of India, Indian Pharmacopoeia Commission, Ministry of Health & Family Welfare, Government of India, Ghaziabad, Uttar Pradesh, India
| | - Ashmita Das
- Department of Pharmacy, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh, 495009, India
| | - Jeevan Lal Prajapati
- Department of Pharmacy, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh, 495009, India
| | - As Pee Singh
- Department of Pharmacy, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh, 495009, India
| | - Surendra H Bodake
- Department of Pharmacy, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh, 495009, India
| | - Kamta P Namdeo
- Department of Pharmacy, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh, 495009, India.
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Wang Z, Wu M, Yang Q. Association between visceral fat area to skeletal muscle mass ratio and hyperuricemia among non-elderly US adults. Nutr Metab Cardiovasc Dis 2025:104106. [PMID: 40345922 DOI: 10.1016/j.numecd.2025.104106] [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: 10/27/2024] [Revised: 04/10/2025] [Accepted: 04/18/2025] [Indexed: 05/11/2025]
Abstract
BACKGROUND AND AIM Sarcopenic visceral obesity is linked to an elevated metabolic risk. Our aim was to explore the possible link between visceral fat area to skeletal muscle mass ratio (VSR) and hyperuricemia risk in non-elderly U.S. adults. METHODS AND RESULTS This cross-sectional study evaluated 5519 non-elderly adults from the National Health and Nutrition Examination Survey (NHANES) database. Visceral fat area (VFA) and appendicular skeletal muscle mass (ASM) were measured using dual-energy X-ray absorptiometry (DXA). Hyperuricemia was identified by serum uric acid (SUA) levels of 7 mg/dL or more in males and 6 mg/dL or more in females. Logistic regression, restricted cubic spline (RCS), and subgroup analyses were applied to investigate the association between VSR and hyperuricemia risk. As VSR levels increase, the prevalence of hyperuricemia becomes more pronounced (6.35 % vs. 14.45 % vs. 14.68 % vs. 17.03 %, P < 0.001). After adjusting for confounding factors, elevated VSR levels are associated with an increased risk of hyperuricemia (OR = 1.136, 95 %CI:1.051-1.229, P = 0.001). Individuals in the fourth quartile of VSR exhibit a higher risk of developing hyperuricemia compared to those in the first quartile (OR = 2.299, 95 %CI:1.328-3.979, P = 0.003). No specific populations were identified in the subgroup analysis. RCS analysis further supports a dose-response relationship. CONCLUSIONS VSR could serve as an epidemiological instrument to assess the impact of sarcopenic visceral obesity on the risk of hyperuricemia.
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Affiliation(s)
- Zhaoxiang Wang
- Department of Endocrinology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, Jiangsu, 215300, China
| | - Menghuan Wu
- Department of Endocrinology, Shanghai Putuo District Liqun Hospital, Shanghai, 200000, China
| | - Qichao Yang
- Department of Endocrinology, Affiliated Wujin Hospital of Jiangsu University, Changzhou, Jiangsu, 213017, China; Department of Endocrinology, Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, 213017, China.
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27
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Wen L, Yang K, Wang J, Zhou H, Ding W. Gut microbiota-mitochondrial crosstalk in obesity: novel mechanistic insights and therapeutic strategies with traditional Chinese medicine. Front Pharmacol 2025; 16:1574887. [PMID: 40331200 PMCID: PMC12052897 DOI: 10.3389/fphar.2025.1574887] [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: 02/11/2025] [Accepted: 03/24/2025] [Indexed: 05/08/2025] Open
Abstract
Obesity rates are rising globally and have become a major public health issue. Recent research emphasizes the bidirectional communication between gut microbiota and mitochondrial function in obesity development. Gut microbiota regulates energy metabolism through metabolites that impact mitochondrial processes, such as oxidative phosphorylation, biogenesis, and autophagy. In turn, alterations in mitochondrial function impact microbiota homeostasis. Traditional Chinese medicine (TCM), which encompasses TCM formulas and the metabolites of botanical drugs, employs a holistic and integrative approach that shows promise in regulating gut microbiota-mitochondrial crosstalk. This review systematically explores the intricate interactions between gut microbiota and mitochondrial function, underscoring their crosstalk as a critical mechanistic axis in obesity pathogenesis. Furthermore, it highlights the potential of TCM in developing innovative, targeted interventions, paving the way for personalized approaches in obesity treatment through the precise modulation of gut microbiota-mitochondrial interactions, offering more effective and individualized therapeutic options.
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Affiliation(s)
| | | | | | | | - Weijun Ding
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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28
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Obrador de Hevia J, López-González ÁA, Ramírez-Manent JI, Paublini H, Tárraga López PJ, Martorell Sánchez C, Riutord-Sbert P. Association Between Alcohol Consumption, Other Healthy Habits and Sociodemographic Variables and the Values of Different Insulin Resistance Risk Scales in 139,634 Spanish Workers. Healthcare (Basel) 2025; 13:921. [PMID: 40281870 PMCID: PMC12026883 DOI: 10.3390/healthcare13080921] [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: 03/18/2025] [Revised: 04/09/2025] [Accepted: 04/14/2025] [Indexed: 04/29/2025] Open
Abstract
Background: Alcohol consumption is a major public health concern, influencing metabolic health and insulin resistance (IR). While moderate alcohol intake has been associated with potential metabolic benefits, excessive consumption is linked to IR and related disorders. This study examines the association between sociodemographic variables, health habits, and IR risk using validated metabolic indices. Methods: A dual-phase study was conducted, including a cross-sectional analysis of 139,634 Spanish workers and a retrospective longitudinal follow-up of 40,431 participants (2009-2019). Data on sociodemographic factors (age, sex and socioeconomic status) and health habits (smoking, alcohol consumption, diet and physical activity) were collected through standardized occupational health assessments. IR risk was assessed using the Triglyceride-Glucose Index (TyG), Metabolic Score for Insulin Resistance (METS-IR), and Single-Point Insulin Sensitivity Estimator (SPISE-IR). Binary logistic regression was used for statistical analysis. Results: Age, male sex, lower socioeconomic status, smoking, alcohol consumption, physical inactivity and low adherence to the Mediterranean diet were significantly associated with higher IR risk across all indices (p < 0.001). Alcohol consumption exhibited a dose-dependent relationship with IR, with excessive intake significantly increasing the risk of IR. Longitudinal data revealed a worsening IR profile over time, particularly among older, low-income and physically inactive individuals. Conclusions: Sociodemographic factors and lifestyle habits strongly influence IR. Preventive strategies focused on reducing alcohol consumption, smoking cessation and promoting physical activity and dietary improvements are essential to mitigate the risk of IR, especially in vulnerable populations. Further longitudinal studies are needed to establish causal relationships and refine intervention strategies.
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Affiliation(s)
- Joan Obrador de Hevia
- ADEMA-Health Group, University Institute of Health Sciences (IUNICS), 07120 Palma, Spain; (J.O.d.H.); (J.I.R.-M.); (H.P.); (C.M.S.); (P.R.-S.)
| | - Ángel Arturo López-González
- ADEMA-Health Group, University Institute of Health Sciences (IUNICS), 07120 Palma, Spain; (J.O.d.H.); (J.I.R.-M.); (H.P.); (C.M.S.); (P.R.-S.)
- Faculty of Dentistry, ADEMA-UIB University School, 07009 Palma, Spain
- Balearic Islands Health Service, 07003 Palma, Spain
- Balearic Islands Health Research Institute Foundation (IDISBA), 07004 Palma, Spain
| | - José Ignacio Ramírez-Manent
- ADEMA-Health Group, University Institute of Health Sciences (IUNICS), 07120 Palma, Spain; (J.O.d.H.); (J.I.R.-M.); (H.P.); (C.M.S.); (P.R.-S.)
- Balearic Islands Health Service, 07003 Palma, Spain
- Balearic Islands Health Research Institute Foundation (IDISBA), 07004 Palma, Spain
- Faculty of Medicine, University of the Balearic Islands, 07122 Palma, Spain
| | - Hernán Paublini
- ADEMA-Health Group, University Institute of Health Sciences (IUNICS), 07120 Palma, Spain; (J.O.d.H.); (J.I.R.-M.); (H.P.); (C.M.S.); (P.R.-S.)
- Faculty of Dentistry, ADEMA-UIB University School, 07009 Palma, Spain
| | | | - Cristina Martorell Sánchez
- ADEMA-Health Group, University Institute of Health Sciences (IUNICS), 07120 Palma, Spain; (J.O.d.H.); (J.I.R.-M.); (H.P.); (C.M.S.); (P.R.-S.)
| | - Pere Riutord-Sbert
- ADEMA-Health Group, University Institute of Health Sciences (IUNICS), 07120 Palma, Spain; (J.O.d.H.); (J.I.R.-M.); (H.P.); (C.M.S.); (P.R.-S.)
- Faculty of Dentistry, ADEMA-UIB University School, 07009 Palma, Spain
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Chen Y, Li Y, Zhang B, Xia W, Feng X. Association between relative fat mass and female infertility among reproductive-aged women from NHANES 2013-2020. Sci Rep 2025; 15:13334. [PMID: 40246879 PMCID: PMC12006307 DOI: 10.1038/s41598-025-97243-5] [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: 08/09/2024] [Accepted: 04/03/2025] [Indexed: 04/19/2025] Open
Abstract
Female infertility is a prevalent condition closely linked with obesity. Current evaluation metrics like body mass index (BMI) and waist circumference (WC) have limitations. Relative fat mass (RFM) is a newer, more accurate obesity metric, but its relationship with infertility lacks research. Data from 3489 female participants aged 18-45 years from the NHANES 2013-2020 cycles were extracted and analyzed. Infertility was assessed based on participants' pregnancy attempts and medical consultations. The primary exposure variables were BMI, WC, and RFM. Survey-weighted logistic regression models were conducted to compare their associations with infertility, expressed as odds ratios (ORs). RFM was further categorized into quartiles for additional regression analysis. Subgroup analyses were conducted to evaluate whether the association between RFM and infertility differs across key demographic and clinical factors, including age, race, PIR, education level, BMI, smoking status, DM, hypertension, age at menarche, and history of pelvic inflammatory disease (PID). Restricted cubic splines (RCS) were employed for robustness and linearity assessments. Our results showed an infertility prevalence of 13.41%, with affected women being older and having higher BMI. The OR (1.039, 95% CI: 1.010, 1.068) for RFM in regression analysis of fully adjusted Model was higher than for BMI (1.020, 95% CI: 1.002, 1.039) and WC (1.014, 95% CI: 1.006, 1.022), indicating that each unit increase in RFM correlates with a higher risk of infertility. Similarly, quartile analysis of fully adjusted Model indicated increased infertility risk with higher RFM quartiles (Q2: OR = 1.66, 95% CI: 1.05, 2.64; Q3: OR = 1.79, 95% CI: 1.16, 2.74; Q4: OR = 2.23, 95% CI: 1.38, 3.60). Additionally, results were consistent in the supplementary subgroup analysis without interaction, and RCS confirmed a linear relationship. Our findings demonstrate a significant association between RFM and female infertility in a population-based sample, supporting the hypothesis that excess adiposity may play a role in reproductive health. Further research is needed to explore the mechanisms and broader applications of RFM in female reproductive health.
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Affiliation(s)
- Yiming Chen
- Department of Urology, The First People'S Hospital of Changzhou, Changzhou, Jiangsu, China
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Yuanyuan Li
- Department of General Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Bo Zhang
- Department of Urology, The First People'S Hospital of Changzhou, Changzhou, Jiangsu, China
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Wei Xia
- Department of Urology, The First People'S Hospital of Changzhou, Changzhou, Jiangsu, China.
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
| | - Xingliang Feng
- Department of Urology, The First People'S Hospital of Changzhou, Changzhou, Jiangsu, China.
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
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Han Y, Gao Y, Qiu M, Wang Y, Li S, Guo M, Zheng T, Liu Z. Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and cerebral atherosclerotic stenosis: a retrospective study. Lipids Health Dis 2025; 24:145. [PMID: 40241203 PMCID: PMC12004609 DOI: 10.1186/s12944-025-02555-0] [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: 02/20/2025] [Accepted: 04/02/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. Early identification of dyslipidemia associated with cerebral atherosclerosis is of great importance for reducing the risk of IS. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a novel lipid biomarker to assess atherosclerosis. The aim of this study is to investigate the association between NHHR and cerebral atherosclerotic stenosis using DSA imaging data, including intracranial/extracranial stenosis, anterior/posterior circulation stenosis, severe stenosis, and symptomatic stenosis. METHODS Patients who underwent DSA examination from July 2022 to December 2024 were included. Participants were divided into four groups based on NHHR levels. Univariable and multivariable logistic regression were applied to assess the association between NHHR and cerebral atherosclerotic stenosis, including intracranial and extracranial stenosis, anterior and posterior circulation stenosis, severe stenosis, and symptomatic stenosis. Restricted cubic splines (RCS) were applied to analyze and visualize the association between NHHR and cerebral atherosclerotic stenosis. RESULTS A total of 853 patients were included in the final analysis. After adjusting for covariables, compared to patients in the lower NHHR groups, those in the higher NHHR groups had a significantly higher occurrence rate of extracranial stenosis, posterior circulation stenosis, severe stenosis, and symptomatic stenosis. Multivariable-adjusted RCS showed a nonlinear association between NHHR and posterior circulation stenosis, and a linear positive association between NHHR and symptomatic stenosis. CONCLUSIONS NHHR may serve as a lipid management indicator for patients with extracranial stenosis, posterior circulation stenosis, severe stenosis, or symptomatic stenosis. NHHR could be an independent risk factor for symptomatic stenosis, which can aid in risk stratification and treatment decision-making for cerebral atherosclerotic stenosis patients.
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Affiliation(s)
- Yating Han
- Department of Neurology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, P. R. China
| | - Yuting Gao
- Department of Neurology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, P. R. China
| | - Mengyuan Qiu
- Department of Neurology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, P. R. China
| | - Yida Wang
- Department of Neurology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, P. R. China
| | - Shenjie Li
- Department of Neurology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, P. R. China
| | - Mengmeng Guo
- Department of Neurology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, P. R. China
| | - Tao Zheng
- Beijing University of Chinese Medicine, No. 11 Beisanhuan East Road, Heping Street, Chaoyang District, Beijing, 100029, China.
| | - Zunjing Liu
- Department of Neurology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, P. R. China.
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Zhou Z, Liu J. Association between body roundness index and incidence of type 2 diabetes in a population-based cohort study. Sci Rep 2025; 15:13186. [PMID: 40240415 PMCID: PMC12003785 DOI: 10.1038/s41598-025-92652-y] [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: 01/13/2025] [Accepted: 03/03/2025] [Indexed: 04/18/2025] Open
Abstract
There is limited national data on the association between body roundness index (BRI) and type 2 diabetes (T2D). A total of 10,785 participants from the China Health and Retirement Longitudinal Study (CHARLS) with repeated BRI measurements from 2011 to 2020 were included. We used Cox proportional hazards model and restricted cubic splines (RCS) to examine the association between BRI and T2D. During a mean follow-up of 7.72 years, 1,653 incident T2D cases were documented. Multivariable Cox proportional hazards regression model demonstrated a significant correlation between the BRI and the risk of T2D. Specifically, every 1-SD increase in BRI corresponded to a 27% heightened risk of T2D (HR: 1.27, 95% CI 1.20-1.35). The analysis also uncovered a non-linear pattern in this relationship, pinpointed by an inflection point at a BRI value of 3.96. Before the inflection point, the HR was 0.85 (95% CI 0.74-0.96), while after the inflection point, the HR increased to 1.29 (95% CI 1.18-1.41). In the middle-aged and elderly Chinese population, elevated BRI was significantly and positively associated with T2D risk. BRI could be a valuable addition to current clinical and public health strategies aimed at reducing the burden of T2D.
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Affiliation(s)
- Zigui Zhou
- School of Exercise and Health, Shanghai University of Sport, 200 Hengren Road, Yangpu, Shanghai, 200438, China
| | - Jingjing Liu
- School of Exercise and Health, Shanghai University of Sport, 200 Hengren Road, Yangpu, Shanghai, 200438, China.
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Kho PF, Wary N, Zanetti D, Abbasi F, Knowles JW, Panyard DJ, Watson KT, RISC Investigators, Stell L, Lazzeroni LC, Gustafsson S, Lind L, Petrie JR, Assimes TL. Cross-sectional, interventional, and causal investigation of insulin sensitivity using plasma proteomics in diverse populations. Metabolism 2025; 169:156263. [PMID: 40221021 DOI: 10.1016/j.metabol.2025.156263] [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: 11/15/2024] [Revised: 03/25/2025] [Accepted: 04/03/2025] [Indexed: 04/14/2025]
Abstract
BACKGROUND We previously reported significant correlations between a direct measure of insulin sensitivity (IS) and blood levels of proteins measured using the Proximity Extension Assay (PEA) in two European cohorts. However, protein correlations with IS within non-European populations, in response to short-term interventions that improve IS, and any causal associations with IS have not yet been established. METHODS We measured 1470 proteins using the PEA in the plasma of 1015 research participants at Stanford University who underwent one or more direct measures of IS. Association analyses were carried out with multivariable linear regression within and across Stanford subgroups and within each of the two European cohorts. Association statistics were also meta-analyzed after transformation and harmonization of the two direct measures of IS. Lastly, we performed genome-wide association studies of IS and used genetic instruments of plasma proteins from the UK Biobank to identify candidate causal proteins for IS through Mendelian Randomization (MR) analysis. RESULTS In age and sex adjusted model, 810 proteins were associated with baseline IS among 652 self-reported European participants in the Stanford cohort at a false discovery rate (FDR) < 0.05. Effect sizes for these proteins were highly correlated with those observed in 122 South Asian, 92 East Asian, 85 Hispanic, and 52 Black/African American persons (r = 0.68 to 0.83, all P ≤ 4.3 × 10-113). Meta-analysis of the full Stanford cohort with the two European cohorts (N = 2945) yielded 247 significant protein associations (FDR < 0.05), with 50 remaining significant after further adjustment for body mass index. In a subset of Stanford participants undergoing insulin sensitizing interventions (N = 53 taking thiazolidinediones, N = 66 with weight loss), 79.3 % of protein level changes were directionally consistent with the respective baseline association (observed/expected p = 6.0 × 10-16). MR analyses identified ten candidate causal proteins for IS, among which were SELE and ASGR1, proteins with established drug targets currently under investigation. CONCLUSION Plasma proteins measured using the PEA provide a robust signature for IS across diverse populations and after short-term insulin sensitizing interventions highlighting their potential value as universal biomarkers of insulin resistance. A small subset of markers provided insights into potential causal molecular mechanisms and therapeutic targets.
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Affiliation(s)
- Pik Fang Kho
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, United States; VA Palo Alto Health Care System, Palo Alto, CA, United States; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
| | - Neil Wary
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, United States
| | - Daniela Zanetti
- Institute of Genetic and Biomedical Research (IRGB), National Research Council (CNR), Cagliari, Italy
| | - Fahim Abbasi
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, United States; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, United States
| | - Joshua W Knowles
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, United States; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, United States; Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, United States
| | - Daniel J Panyard
- VA Palo Alto Health Care System, Palo Alto, CA, United States; Department of Genetics, Stanford University School of Medicine, Stanford, CA, United States
| | - Katie T Watson
- Department of Psychiatry, Stanford University School of Medicine, United States
| | | | - Laurel Stell
- VA Palo Alto Health Care System, Palo Alto, CA, United States; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, United States
| | - Laura C Lazzeroni
- Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, United States; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States
| | | | - Lars Lind
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - John R Petrie
- School of Health and Wellbeing, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Themistocles L Assimes
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, United States; VA Palo Alto Health Care System, Palo Alto, CA, United States; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, United States; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, United States.
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Konończuk K, Muszyńska-Rosłan K, Konstantynowicz-Nowicka K, Chabowski A, Latoch E. Altered free fatty acids levels and the onset of metabolic syndrome in childhood cancer survivors. Nutrition 2025; 136:112799. [PMID: 40373356 DOI: 10.1016/j.nut.2025.112799] [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: 10/26/2024] [Revised: 03/26/2025] [Accepted: 04/07/2025] [Indexed: 05/17/2025]
Abstract
Childhood cancer survivors (CCS) are at increased risk for various health issues, including obesity, insulin resistance, hypertension, and dyslipidemia, resulting in the development of metabolic syndrome (MetS) later in life. It has been suggested that anticancer treatment may lead to alterations in lipid metabolism, which play a role in the pathogenesis of metabolic syndrome among CCS. The prospective study included 110 CCS, with a follow-up time of 6.39 years since the end of treatment. Fasting serum of fourteen fatty acids concentrations were measured in all children using gas-liquid chromatography. Among the study group, 41 CCS (37%) met 1 or more criteria for metabolic syndrome and exhibited higher concentrations of myristic (P = 0.002), palmitic (P = 0.003), stearic (P = 0.017), oleic (P = 0. 019), arachidonic (P = 0.002), lignoceric (P = 0.005), docosahexaenoic (P = 0.005), and total fatty acids compared to CCS without metabolic syndrome factors. Additionally, overweight or obese CCS presented higher levels of myristic (P = 0.048), palmitic (P = 0.016), oleopalmitic (P = 0.019), stearic (P = 0.024), oleic (P = 0.020), α-linoleic (P = 0.023) and behenic (P = 0.036) acids compared to survivors with a normal BMI. Childhood cancer survivors develop abnormalities in lipid metabolism, which may contribute to an earlier onset of metabolic syndrome. Additionally, overweight or obesity significantly exacerbates changes in lipid metabolism.
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Affiliation(s)
- Katarzyna Konończuk
- Department of Paediatrics, Oncology and Hematology, Medical University of Bialystok, Bialystok, Poland.
| | | | | | - Adrian Chabowski
- Department of Physiology, Medical University of Bialystok, Bialystok, Poland
| | - Eryk Latoch
- Department of Paediatrics, Oncology and Hematology, Medical University of Bialystok, Bialystok, Poland
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Sharma S, Tiwari N, Tanwar SS. The current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04069-z. [PMID: 40202676 DOI: 10.1007/s00210-025-04069-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 03/17/2025] [Indexed: 04/10/2025]
Abstract
Recent research has highlighted the complex relationship between gut microbiota, metabolic pathways, and nonalcoholic fatty liver disease (NAFLD) progression. Gut dysbiosis, commonly observed in NAFLD patients, impairs intestinal permeability, leading to the translocation of bacterial products like lipopolysaccharides, short-chain fatty acids, and ethanol to the liver. These microbiome-associated mechanisms contribute to intestinal and hepatic inflammation, potentially advancing NAFLD to NASH. Dietary habits, particularly those rich in saturated fats and fructose, can modify the microbiome composition, leading to dysbiosis and fatty liver development. Metabolomic approaches have identified unique profiles in NASH patients, with specific metabolites like ethanol linked to disease progression. While bariatric surgery has shown promise in preventing NAFLD progression, the role of gut microbiome and metabolites in this improvement remains to be proven. Understanding these microbiome-related pathways may provide new diagnostic and therapeutic targets for NAFLD and NASH. A comprehensive review of current literature was conducted using multiple medical research databases, including PubMed, Scopus, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, ScienceDirect, Medline, ProQuest, and Google Scholar. The review focused on studies that examine the relationship between gut microbiota composition, metabolic pathways, and NAFLD progression. Key areas of interest included microbial dysbiosis, endotoxin production, and the influence of diet on gut microbiota. The analysis revealed that gut dysbiosis contributes to NAFLD through several mechanisms, diet significantly influences gut microbiota composition, which in turn affects liver function through the gut-liver axis. High-fat diets can lead to dysbiosis, altering microbial metabolic activities and promoting liver inflammation. Specifically, gut microbiota-mediated generation of saturated fatty acids, such as palmitic acid, can activate liver macrophages and increase TNF-α expression, contributing to NASH development. Different dietary components, including cholesterol, fiber, fat, and carbohydrates, can modulate the gut microbiome and influence NAFLD progression. This gut-liver axis plays a crucial role in maintaining immune homeostasis, with the liver responding to gut-derived bacteria by activating innate and adaptive immune responses. Microbial metabolites, such as bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis, contributing to NASH pathogenesis. Additionally, the microbiome of NASH patients shows an elevated capacity for alcohol production, suggesting similarities between alcoholic steatohepatitis and NASH. These findings indicate that targeting the gut microbiota may be a promising approach for NASH treatment and prevention. Recent research highlights the potential of targeting gut microbiota for managing nonalcoholic fatty liver disease (NAFLD). The gut-liver axis plays a crucial role in NAFLD pathophysiology, with dysbiosis contributing to disease progression. Various therapeutic approaches aimed at modulating gut microbiota have shown promise, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Probiotics have demonstrated efficacy in human randomized controlled trials, while other interventions require further investigation in clinical settings. These microbiota-targeted therapies may improve NAFLD outcomes through multiple mechanisms, such as reducing inflammation and enhancing metabolic function. Although lifestyle modifications remain the primary recommendation for NAFLD management, microbiota-focused interventions offer a promising alternative for patients struggling to achieve weight loss targets.
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Affiliation(s)
- Seema Sharma
- Department of Pharmacy, Shri Vaishnav Vidyapeeth Vishwavidyalaya, Indore, M.P, India
| | - Nishant Tiwari
- Acropolis Institute of Pharmaceutical Education and Research, Indore, M.P, India
| | - Sampat Singh Tanwar
- Department of Pharmacy, Shri Vaishnav Vidyapeeth Vishwavidyalaya, Indore, M.P, India.
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Lin M, Chen X, Wu M, Xiao J, Li S, Tang H, Tan X, Chen Y. Interactive effects of abdominal obesity and insulin resistance on cardiometabolic risk. REVISTA ESPANOLA DE CARDIOLOGIA (ENGLISH ED.) 2025:S1885-5857(25)00112-4. [PMID: 40194760 DOI: 10.1016/j.rec.2025.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 03/17/2025] [Indexed: 04/09/2025]
Abstract
INTRODUCTION AND OBJECTIVES Both abdominal obesity (AO) and insulin resistance (IR) are predictors of cardiometabolic disease (CMD). We aimed to evaluate the temporal relationship between AO and IR and their combined effect on CMD risk. METHODS A nationally representative cohort of 9234 participants was included, with a maximum follow-up of 9 years. The triglyceride-glucose (TyG) index was calculated as an indicator of IR, and AO was measured by waist circumference (WC). Cox regression was applied to evaluate the combined effect of AO and TyG on CMD risk, including hypertension, diabetes, heart disease, and stroke. A cross-lagged panel model was used to examine the temporal relationship. Multiplicative and additive interactions between AO and insulin resistance, as well as the mediating effect of TyG, were assessed. RESULTS Individuals concurrently with AO and higher TyG (≥8.6 [median]) had the highest risk of hypertension (HR,1.46; 95%CI, 1.25-1.69), diabetes (HR, 1.99; 95%CI, 1.65-2.41), and stroke (HR, 1.76; 95%CI, 1.22-1.94). A biological interaction between AO and IR on diabetes was observed, with the attributable proportion due to interaction being 29%. There was a bidirectional temporal relationship between WC and TyG, and the effect of WC on TyG was more prominent than vice versa. High TyG had a mediating effect on the association of AO with hypertension (19%), diabetes (25%), and stroke (24%). CONCLUSIONS The findings reveal a temporal relationship between AO and IR, their combined effect on hypertension, diabetes, and stroke, and the mediating role of IR. Strategies simultaneously targeting both factors should be emphasized for the primary prevention of CMD.
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Affiliation(s)
- Mengyue Lin
- Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Human Phenome Institute of Shantou University Medical College, Guangdong Engineering Research Centre of Human Phenome, Chemistry and Chemical Engineering Guangdong Laboratory, Shantou, Guangdong, China; Clinical Medical Research Center, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Xiaocong Chen
- Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Muli Wu
- Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Jiaxin Xiao
- Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Shaobin Li
- Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Haoxian Tang
- Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Xuerui Tan
- Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Human Phenome Institute of Shantou University Medical College, Guangdong Engineering Research Centre of Human Phenome, Chemistry and Chemical Engineering Guangdong Laboratory, Shantou, Guangdong, China; Clinical Medical Research Center, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
| | - Yequn Chen
- Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Human Phenome Institute of Shantou University Medical College, Guangdong Engineering Research Centre of Human Phenome, Chemistry and Chemical Engineering Guangdong Laboratory, Shantou, Guangdong, China; Clinical Medical Research Center, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
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Zheng H, Wu B, Zhuang C, Mao J, Li M, Luo Y, Huang L, Lin S, Zhao F, Hu Y. Cardiometabolic index as a predictor of gallstone risk: evidence from NHANES 2017-2020. BMC Gastroenterol 2025; 25:218. [PMID: 40181266 PMCID: PMC11966856 DOI: 10.1186/s12876-025-03777-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 03/12/2025] [Indexed: 04/05/2025] Open
Abstract
BACKGROUND The Cardiometabolic Index (CMI), a composite marker integrating lipid profiles (triglycerides-to-HDL-C ratio) and abdominal obesity (waist-to-height ratio), we aimed to assess its association with gallstone prevalence. METHODS We analyzed data from 2,692 participants in the NHANES 2017-2020 dataset. Gallstones were identified through self-reported data, which may introduce bias in the diagnosis. This limitation should be considered when interpreting the results. Logistic regression modelling, smoothed curve fitting and threshold effect analysis assessed the association between CMI and gallstones. RESULT Higher CMI was significantly associated with an increased risk of gallstones (OR = 1.90, 95% CI: 1.37-2.62, P < 0.0001). A threshold effect was observed at CMI = 0.85, below which risk increased significantly (OR = 2.62, 95% CI:1.34-5.12, P = 0.0049), but became non-significant above this value. The association was stronger in women. CONCLUSION Our findings support the use of CMI as a potential predictive marker for gallstone risk, suggesting its integration into clinical assessments for early detection and prevention.
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Affiliation(s)
- Huachao Zheng
- Department of General Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, Zhejiang, China
| | - Bo Wu
- Department of General Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, Zhejiang, China
| | - Caixiang Zhuang
- Department of Neurology, Postgraduate Training Base Alliance of Wenzhou Medical University (WenzhouPeople's Hospital), Wenzhou, Zhejiang, China
| | - Jiesheng Mao
- Department of Neurology, Postgraduate Training Base Alliance of Wenzhou Medical University (WenzhouPeople's Hospital), Wenzhou, Zhejiang, China
| | - Min Li
- Department of General Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, Zhejiang, China
| | - Yuncheng Luo
- Department of General Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, Zhejiang, China
| | - Lidong Huang
- Department of General Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, Zhejiang, China
| | - Sisi Lin
- Department of General Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, Zhejiang, China
| | - Feiyang Zhao
- Department of General Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, Zhejiang, China
| | - Yiren Hu
- Department of General Surgery, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, Zhejiang, China.
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Song Z, Miao X, Liu S, Hu M, Xie X, Sun Y, Leng S. Associations between cardiometabolic indices and the onset of metabolic dysfunction-associated steatotic liver disease as well as its progression to liver fibrosis: a cohort study. Cardiovasc Diabetol 2025; 24:154. [PMID: 40181314 PMCID: PMC11969729 DOI: 10.1186/s12933-025-02716-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Accepted: 03/27/2025] [Indexed: 04/05/2025] Open
Abstract
BACKGROUND This study sought to examine the associations between cardiometabolic indices and the onset of metabolic dysfunction-associated steatotic liver disease (MASLD) as well as its progression to liver fibrosis. METHODS This study comprised 25,366 subjects aged 18 years and older, free of MASLD at baseline, from the Dalian Health Management Cohort (DHMC). Cardiometabolic indices include cardiometabolic index (CMI), atherogenic index of plasma (AIP), triglyceride glucose (TyG), triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist circumference (TyG-WC) and triglyceride glucose-waist height ratio (TyG-WHtR). All participants were categorized into quartile groups based on cardiometabolic indices. Cox proportional hazards regression models and restricted cubic splines were employed to examine the relationship between cardiometabolic indices and the incidence of MASLD as well as its progression to liver fibrosis, and analyses were performed between different subgroups. Mediation analysis was employed to explore how obesity and inflammation serve as mediators in the connection between cardiometabolic indices and MASLD. To evaluate the predictive ability of cardiometabolic indices for the onset of MASLD, the time-dependent receiver operating characteristic (ROC) curve was utilized. RESULTS A total of 5378 (21.2%) individuals developed MASLD during the follow-up period of 82,445 person-years. Multivariates Cox regression analyses showed that participants in the highest quartile of cardiometabolic indices had greater risk of MASLD than those in the lowest quartile (CMI: HR = 6.11, 95% CI 5.45-6.86; AIP: HR = 4.58, 95% CI 4.11-5.10; TyG: HR = 3.55, 95% CI 3.21-3.92; TyG-BMI: HR = 13.55, 95% CI 11.80-15.57; TyG-WC: HR = 12.52, 95% CI 10.93-14.34; TyG-WHtR: HR = 11.37, 95% CI 9.96-12.98). TyG-BMI (HR = 1.36, 95% CI 1.18-1.57), but not other cardiometabolic indices, was associated with liver fibrosis. Mediation analysis indicated that BMI mediated 40.4%, 33.2%, 36.5%, - 10.4%, 37.4%, 48.5% of the associations between CMI, AIP, TyG, TyG-BMI, TyG-WC, TyG-WHtR and MASLD. Time-dependent ROC curves demonstrated that TyG-BMI had a superior predictive ability for MASLD onset compared to other indicators. CONCLUSIONS The risk of developing MASLD increases as the level of cardiometabolic indices increases. Obesity may serve as a mediating factor in the aforementioned association. TyG-BMI showed the strongest association with the onset of MASLD and its progression to liver fibrosis, proved to be outperformed other cardiometabolic indicators, and could be the best clinical non-invasive biomarker for early screening of MASLD and liver fibrosis.
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Affiliation(s)
- Ziping Song
- Health Management Center, The Second Hospital of Dalian Medical University, No.467, Zhongshan Road, Dalian, 116023, China
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Xinlei Miao
- Health Management Center, The Second Hospital of Dalian Medical University, No.467, Zhongshan Road, Dalian, 116023, China
| | - Shuang Liu
- School of Public Health, Dalian Medical University, Dalian, 116044, Liaoning, China
| | - Manling Hu
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Xiaoling Xie
- School of Public Health, Dalian Medical University, Dalian, 116044, Liaoning, China
| | - Yuting Sun
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Song Leng
- Health Management Center, The Second Hospital of Dalian Medical University, No.467, Zhongshan Road, Dalian, 116023, China.
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China.
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Forst T, De Block C, Del Prato S, Frias J, Lautenbach A, Ludvik B, Marinez M, Mathieu C, Müller TD, Schnell O. Novel pharmacotherapies for weight loss: Understanding the role of incretins to enable weight loss and improved health outcomes. Diabetes Obes Metab 2025; 27 Suppl 2:48-65. [PMID: 39931897 DOI: 10.1111/dom.16247] [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: 11/26/2024] [Revised: 01/25/2025] [Accepted: 01/26/2025] [Indexed: 04/17/2025]
Abstract
Obesity and type 2 diabetes mellitus (T2D) are widespread diseases that significantly impact cardiovascular and renal morbidity and mortality. In the recent years, intensive research has been performed to assess the role of adipose tissue and body fat distribution in the development of metabolic and non-metabolic complications in individuals with obesity. In addition to lifestyle modifications, glucagon-like peptide-1 receptor agonists (GLP-1-RA) have become a meaningful treatment expansion for the management of both disorders. In addition to improving metabolic control and reducing body weight, treatment with GLP-1-RAs reduces cardiovascular and renal events in individuals with obesity with and without diabetes. These important benefits of GLP-1-RAs have triggered new interest in other enteroendocrine and enteropancreatic peptides for treating obesity and its metabolic and non-metabolic consequences. The first peptide dual-agonist targeting glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors has been approved for the treatment of T2D and obesity. GIP/GLP-1 dual-agonism appear to provide better metabolic control and greater weight reduction compared with GLP-1-R mono-agonism. Other peptide and non-peptide co-agonists are in clinical development for obesity, T2D, metabolic dysfunction-associated steatotic liver disease (MASLD) and other metabolic disorders. This narrative review aims to summarize the available data on approved and emerging enteroendocrine and enteropancreatic based treatment approaches for obesity and metabolic disorders. In addition to available clinical efficacy measures, side effects, limitations and open challenges will also be addressed.
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Affiliation(s)
- Thomas Forst
- CRS Clinical Research Services GmbH, Mannheim, Germany
| | - Christophe De Block
- Department of Endocrinology-Diabetology, Antwerp University Hospital and University of Antwerp, Belgium
| | - Stefano Del Prato
- Interdisciplinary Research Center "Health Science," Sant'Anna School of Advanced Studies, Pisa, Italy
| | - Juan Frias
- Biomea Fusion, Redwood City, California, USA
| | - Anne Lautenbach
- University Medical-Center Hamburg-Eppendorf, Hamburg, Germany
| | - Bernhard Ludvik
- Landstrasse Clinic and Karl Landsteiner Institute for Obesity and Metabolic Disorders, Vienna, Austria
| | | | | | - Timo D Müller
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Munich, Neuherberg, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Walther-Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität München (LMU), Munich, Germany
| | - Oliver Schnell
- Forschergruppe Diabetes E.V. at the Helmholtz Center Munich, Munich, Germany
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Hou D, Liu S, Sun Y, Liu C, Shang X, Pei L, Chen G. Estimated Glucose Disposal Rate Associated With Risk of Frailty and Likelihood of Reversion. J Cachexia Sarcopenia Muscle 2025; 16:e13814. [PMID: 40245241 PMCID: PMC12005398 DOI: 10.1002/jcsm.13814] [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: 09/09/2024] [Revised: 02/28/2025] [Accepted: 03/25/2025] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND Estimated glucose disposal rate (eGDR) is a simple and effective measure for insulin resistance, which is associated with higher risk of frailty. We aim to analyse the associations of eGDR with frailty risk and its reversibility. METHODS A population-based longitudinal study was conducted of 11 670 participants from the China Health and Retirement Longitudinal Study and 19 355 participants from the Health and Retirement Study. Frailty was assessed by the frailty index and reversibility was measured by transitions from frailty at baseline to non-frailty during follow-up. The eGDR was divided into Q1, Q2, Q3 and Q4 according to the quartiles. Multi-state Markov model was performed to evaluate the effects of eGDR on transitions among non-frailty, frailty and death. Cox regression model was used to estimate eGDR associated with the risk of frailty and the likelihood of reversion. RESULTS In Chinese population characterized by a median age of 60 years (IQR: 54-66) with 6119 women (52.43%), compared with the Q1 level of eGDR, participants exposure to Q3 and Q4 level decreased the probability of transitioning from non-frailty to frailty by 22% (HR = 0.78, 95% CI: 0.69-0.88) and 25% (HR = 0.75, 95% CI: 0.66-0.86), respectively. But its Q2, Q3 and Q4 levels increased the probability of transitioning from frailty to non-frailty by 24% (HR = 1.24, 95% CI: 1.06-1.44), 39% (HR = 1.39, 95% CI: 1.19-1.64) and 33% (HR = 1.33, 95% CI: 1.13-1.58). In American population with a median age of 63 years (IQR: 56-72) and 11 189 women (57.81%), its Q2, Q3 and Q4 levels decreased the probability of transitioning from non-frailty to frailty by 17% (HR = 0.83, 95% CI: 0.77-0.89), 24% (HR = 0.76, 95% CI: 0.70-0.82) and 46% (HR = 0.54, 95% CI: 0.49-0.59), respectively. The probability of revising frailty increased by 25% (HR = 1.25, 95% CI: 1.13-1.38), 36% (HR = 1.36, 95% CI: 1.22-1.51) and 48% (HR = 1.48, 95% CI: 1.30-1.69) for levels Q2, Q3 and Q4. As shown in the prospective analysis, increased eGDR levels from Q2 to Q4 were associated with decreased frailty risk and higher likelihood of reversion, as evidenced by the dose-response relationship revealed by restricted cubic spline analysis. CONCLUSIONS Higher levels of eGDR were associated with a reduced risk of frailty, delayed transition from non-frailty to frailty and an increased likelihood of reversion. eGDR emerges as a promising predictor for early frailty detection, prognosis assessment and a potential therapeutic target for intervention strategies.
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Affiliation(s)
- Dingchun Hou
- Institute of Population ResearchPeking UniversityBeijingChina
| | - Shangjun Liu
- Institute of Population ResearchPeking UniversityBeijingChina
| | - Yumei Sun
- School of NursingPeking UniversityBeijingChina
| | - Chang Liu
- School of Sport ScienceBeijing Sport UniversityBeijingChina
| | - Xue Shang
- School of NursingPeking UniversityBeijingChina
| | - Lijun Pei
- Institute of Population ResearchPeking UniversityBeijingChina
| | - Gong Chen
- Institute of Population ResearchPeking UniversityBeijingChina
- Institute of Ageing StudiesPeking UniversityBeijingChina
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Pan C, Yang Y, Zhao Z, Hu J. Combined effects of natural products and exercise on apoptosis pathways in obesity-related skeletal muscle dysfunction. Apoptosis 2025; 30:537-552. [PMID: 39833631 DOI: 10.1007/s10495-024-02069-7] [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] [Accepted: 12/23/2024] [Indexed: 01/22/2025]
Abstract
Obesity and related metabolic disorders are closely linked to increased apoptosis in skeletal muscle, leading to muscle degeneration, insulin resistance, and the progression of diseases such as type 2 diabetes and sarcopenia. This review explores the combined effects of natural products, including resveratrol, curcumin, and quercetin, and physical exercise on modulating apoptosis pathways in skeletal muscle. Both natural products and regular physical activity independently reduce oxidative stress and improve mitochondrial function, thereby regulating the balance between pro-apoptotic and anti-apoptotic signals. When combined, these interventions amplify their protective effects on muscle health, promoting mitochondrial biogenesis, reducing apoptosis, and enhancing muscle regeneration. This review also discusses the molecular mechanisms by which these strategies influence apoptosis, with a focus on the Bcl-2 pathway, and explores the clinical implications for the prevention and treatment of obesity-related diseases. The synergistic benefits of combining exercise with natural product supplementation offer a promising therapeutic approach for managing metabolic disorders, preserving muscle function, and improving overall metabolic health.
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Affiliation(s)
- Chun Pan
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, Guizhou, China
| | - Yiying Yang
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, Guizhou, China
| | - Zailin Zhao
- School of Law, Guizhou University, Guiyang, 550025, Guizhou, China
| | - Jingye Hu
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, Guizhou, China.
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Rai V, Deepu V, Agrawal DK. Targeting RAGE-signaling pathways in the repair of rotator-cuff injury. Mol Cell Biochem 2025; 480:2539-2554. [PMID: 39395136 PMCID: PMC11961478 DOI: 10.1007/s11010-024-05132-8] [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: 04/12/2024] [Accepted: 10/01/2024] [Indexed: 10/14/2024]
Abstract
Rotator cuff injury (RCI) is a common musculoskeletal problem that can have a significant impact on the quality of life and functional abilities of those affected. Novel therapies, including proteomics-based, stem cells, platelet-rich plasma, and exosomes, are being developed to promote rotator-cuff healing. The receptor for advanced glycation end-products (RAGE) is a multifunctional receptor that is expressed on several cell types and is implicated in several physiologic and pathological processes, such as tissue repair, inflammation, and degeneration. Because of its capacity to bind with a variety of ligands and initiate signaling pathways that lead to inflammatory responses in RCI, RAGE plays a crucial role in inflammation. In this critical review article, we discussed the role of RAGE-mediated persistent inflammation in RCI followed by novel factors including PKCs, TIRAP, DIAPH1, and factors related to muscle injury with their therapeutic potential in RCI. These factors involve various aspects of muscle injury and signaling and the possibility of targeting these factors to improve the clinical outcomes in RCI still needs further investigation.
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Affiliation(s)
- Vikrant Rai
- Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766-1854, USA
| | - Vinitha Deepu
- Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766-1854, USA
| | - Devendra K Agrawal
- Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766-1854, USA.
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Bahrizadeh M, Fotros D, Chegini M, Sadeghi A, Hekmatdoost A, Yari Z. Association of dietary glycemic index and glycemic load with pancreatic steatosis: a case control study. BMC Endocr Disord 2025; 25:89. [PMID: 40165222 PMCID: PMC11956228 DOI: 10.1186/s12902-025-01909-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 03/17/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Carbohydrate intake, its type and characteristics including glycemic index (GI) and glycemic load (GL) may be associated with the risk of pancreatic steatosis (PS), but there is no conclusive evidence. The aim of the present study was to investigate whether the intake of carbohydrates, GI and GL were associated with an increased risk of PS. METHODS To conduct this study, 278 patients with common bile duct stones (CBD) underwent endoscopic ultrasound, including 89 patients with PS (case group) and 189 healthy individuals (control group). In addition to demographic and anthropometric information, a 168-item questionnaire of food frequency was completed to calculate GL and GI. RESULTS With the increase of GI and GL, the number of patients with PS increased significantly (P = 0.013, P < 0.001, respectively) and the risk of PS increased significantly. A similar increase in risk of PS was found with increased risk of carbohydrate, simple sugar and fructose intake. After adjusting all the confounders, the risk of PS with increasing simple sugar and fructose intake was 4.3 times (OR T3 vs. T1 = 4.3, 95% CI: 1.7-10.6, P trend < 0.001) and 5.3 times (OR T3 vs. T1 = 5.3, 95% CI: 2.2-12.9, P trend < 0.001), respectively, compared to the first tertile. Conversely, increased fiber intake showed a reverse association with the PS, so that those in the second and third tertiles of fiber intake were 84% (OR = 0.16, 95% CI: 0.05-0.45) and 87% (OR = 0.13, 95% CI: 0.04-0.39) less at risk of developing PS, respectively (P trend = 0.001). CONCLUSIONS These findings support the hypothesis of direct associations between GI and GL increased risk of PS.
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Affiliation(s)
- Mohammad Bahrizadeh
- Student Research Committee, Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran
| | - Danial Fotros
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran
| | - Maedeh Chegini
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran
| | - Amir Sadeghi
- Research Institute for Gastroenterology and Liver Diseases of Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran.
| | - Zahra Yari
- Department of Nutrition Research, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran.
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Wang Y, Chen B, Zang C, Hou J. Association between cumulative average triglyceride glucose-body mass index and the risk of CKD onset. Front Endocrinol (Lausanne) 2025; 16:1525078. [PMID: 40230478 PMCID: PMC11994409 DOI: 10.3389/fendo.2025.1525078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 03/10/2025] [Indexed: 04/16/2025] Open
Abstract
Background Chronic kidney disease (CKD) has become a significant global public health challenge, which was reported to be highly correlated with the triglyceride glucose-body mass index (TyG-BMI). Nevertheless, literature exploring the association between changes in the TyG-BMI and CKD incidence is scant, with most studies focusing on individual values of the TyG-BMI. We aimed to investigate whether cumulative average in the TyG-BMI were associated with CKD incidence. Methods Data in our study were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. The exposure was the cumulative average TyG-BMI from 2011 to 2015. The TyG-BMI was calculated by the formula ln [TG (mg/dl) × FBG (mg/dl)/2] × BMI (kg/m2), and the cumulative average TyG-BMI was calculated as follows: (TyG-BMI2011+ TyG-BMI2015)/2. Logistic regressions were used to determine the association between different quartiles of cumulative average TyG-BMI and CKD incidence. Meanwhile, restricted cubic spline was applied to examine the potential nonlinear association of the cumulative average TyG-BMI and CKD incidence. In addition, subgroup analysis was used to test the robustness of results. Results Of the 6117 participants (mean [SD] age at baseline, 58.64 [8.61] years), 2793 (45.7%) were men. During the 4 years of follow-up, 470 (7.7%) incident CKD cases were identified. After adjusting for potential confounders, compared to the participants in the lowest quartile of cumulative average TyG-BMI, participants in the 3rd and 4th quartile had a higher risk of CKD onset. The ORs and 95%CIs were [1.509(1.147, 1.990)] and [1.452(1.085, 1.948)] respectively. In addition, restricted cubic spline showed the cumulative average TyG-BMI had a liner association (p-nonlinear = 0.139). Conclusions The cumulative average in the TyG-BMI was independently associated with the risk of CKD in middle-aged and older adults. Monitoring long-term changes in the TyG-BMI may assist with the early identification of individuals at high risk of CKD.
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Affiliation(s)
| | | | | | - Jie Hou
- Department of Nephrology, the First Hospital of Jilin University, Changchun, Jilin, China
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Zhang Y, Tang Y, Xu L, Fang L, Li X, Mao W, Liu T. Effect of limb ischemic preconditioning on the indirect index of insulin resistance in maintenance hemodialysis patients. BMC Cardiovasc Disord 2025; 25:238. [PMID: 40158091 PMCID: PMC11954303 DOI: 10.1186/s12872-025-04677-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 03/17/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND Poor prognosis of maintenance hemodialysis (MHD) patients, including cardiovascular disease (CVD) and protein-energy wasting (PEW), is strongly associated with insulin resistance (IR). Previous studies have revealed that limb ischemic preconditioning (LIPC), as an intervention, is effective in reducing inflammation and oxidative stress levels in patients. The aim of this study was to elucidate the effects of LIPC on IR indirect indices, inflammation and oxidative stress indices, and to further explore the potential mechanisms of LIPC in reducing IR indices. METHODS A retrospective analysis was performed on 62 patients with MHD who had previously undergone limb ischemia preconditioning (LIPC) or sham surgery (Sham). General clinical and laboratory data were collected. Furthermore, to assess the IR status of MHD patients, the following indices were employed: triglyceride-glucose index (TyG), triglyceride-glucose body mass index (TyG-BMI), triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C), and metabolic score of insulin resistance (METS-IR). Inflammation and oxidative stress indicators included high-sensitivity C-reactive protein (hs-CRP), hs-CRP /albumin ratio (CAR), serum malondialdehyde (MDA) and superoxide dismutase (SOD). Mediation analysis was conducted using Model 4 in the SPSS PROCESS macro version 4.1. RESULTS Following a four-week experiment, hs-CRP (15.46 ± 3.60 vs. 10.53 ± 5.42, p < 0.001), CAR (0.39 ± 0.10 vs. 0.26 ± 0.13, p < 0.001) and MDA (8.46(6.71,9.85) vs. 5.99(5.11,7.89), p = 0.001) indices were significantly decreased in the MHD patients of the LIPC group, whereas SOD indices (215.07(180.27,286.45) vs. 267.76(228.32,319.54), p = 0.012) were significantly higher. Only hs-CRP (-4.93 ± 5.68 vs. 0.16 ± 5.39, p = 0.001) and CAR (-0.14 ± 0.14 vs. -0.001 ± 0.15, p = 0.001) were significantly different in the LIPC group compared to the Sham group. In contrast, the changes in MDA (p = 0.058) and SOD (p = 0.107) were not statistically significant between groups. The intra- and inter-group differences in the four indirect indices of IR were significant (p < 0.05). The heatmap revealed a notable correlation between the changes in hs-CRP and CAR levels and the changes in the IR indirect indices. In addition, The mediation model showed that the inflammatory indicators hs-CRP played a partial mediating role in the improvement of IR indices (TyG-BMI) by LIPC. CONCLUSION LIPC has an excellent ability to inhibit inflammation and peroxidation. In addition, in MHD patients, inflammation plays a significant role in the process of LIPC improving IR index.
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Affiliation(s)
- Yu Zhang
- Department of Nephrology, The Second People's Hospital of Changzhou, Third Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Yushang Tang
- Department of Nephrology, The Second People's Hospital of Changzhou, Third Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Linfang Xu
- Department of Nephrology, The Second People's Hospital of Changzhou, Third Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Li Fang
- Department of Nephrology, The Second People's Hospital of Changzhou, Third Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Xiaoping Li
- Department of Nephrology, The Second People's Hospital of Changzhou, Third Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Wenbin Mao
- Department of Nephrology, The Second People's Hospital of Changzhou, Third Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Tongqiang Liu
- Department of Nephrology, The Second People's Hospital of Changzhou, Third Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, China.
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Almeida APD, Lopes LJ, Bersch-Ferreira ÂC, Torreglosa CR, Marcadenti A, Weber B, Bressan J, Hermsdorff HHM. Insulin resistance mediate the association between leucine intake, dietary glycemic index, and type 2 diabetes in secondary cardiovascular prevention: path analysis from Brazilian cardioprotective nutritional (BALANCE) program. Eur J Nutr 2025; 64:140. [PMID: 40156624 DOI: 10.1007/s00394-025-03653-6] [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: 03/06/2024] [Accepted: 03/16/2025] [Indexed: 04/01/2025]
Abstract
PURPOSE Insulin resistance (IR) is an important mediator of the relationship between food intake and the development of type 2 diabetes mellitus (T2DM). Most of the few studies that have evaluated this relationship relied on the triglyceride-glucose index (TyG index) tool. Here, we evaluated the association between leucine intake, glycemic index, and T2DM with related mediators in individuals throughout secondary cardiovascular prevention. METHODS Sociodemographic, anthropometric, clinical, and food intake data were recorded from the baseline of the trial Brazilian Cardioprotective Nutritional (BALANCE) Program. Path analysis was used to explore the relationships between variables. RESULTS This study enrolled 2,247 participants (median age of 63.0 (45-91) years; 58.8% males). The TyG index showed positive association with T2DM (SC = 0.356; p < 0.001) and negative association with leucine intake (SC= -0.046; p = 0.028). The glycemic index (GI) was positively associated with BMI (SC = 0.072; p = 0.001), and BMI had an indirect positive effect on T2DM mediated by the TyG index (SC = 0.078; p < 0.001). Leucine intake had indirect negative effect on T2DM, mediated by the TyG index (SC= -0.016; p = 0.029), while GI had indirect positive effect on T2DM mediated by BMI and TyG index (SC = 0.006; p = 0.002). CONCLUSION Leucine intake and GI showed indirect association with T2DM, mediated by TyG and BMI, in individuals on secondary cardiology prevention, reinforcing the importance of assessing food consumption and promotin food quality improvements for cardiometabolic control by different pathways. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER NCT01620398. Registered 15 June 2012.
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Affiliation(s)
- Alinne Paula de Almeida
- Laboratory of Clinical Analysis and Genomics, Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, MG, Brasil
- Laboratory of Energy Metabolism and Body Composition, Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, MG, Brasil
| | - Leidjaira Juvanhol Lopes
- Laboratory of Nutritional Epidemiology and Health Surveillance, Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, MG, Brasil
| | | | | | - Aline Marcadenti
- Hcor Research Institute, HCor (IP-Hcor), São Paulo, SP, Brasil
- Graduate Program in Health Sciences (Cardiology), Instituto de Cardiologia/Fundacao Universitária de Cardiologia do Rio Grande do Sul, Porto Alegre, RS, Brasil
- Graduate Program in Epidemiology, Faculty of Health Public, Universidade de São Paulo, São Paulo, SP, Brasil
| | - Bernardete Weber
- Real e Benemérita Associação Portuguesa de Beneficência, São Paulo, SP, Brasil
- Hcor Research Institute, HCor (IP-Hcor), São Paulo, SP, Brasil
| | - Josefina Bressan
- Laboratory of Clinical Analysis and Genomics, Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, MG, Brasil
- Laboratory of Energy Metabolism and Body Composition, Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, MG, Brasil
| | - Helen Hermana Miranda Hermsdorff
- Laboratory of Clinical Analysis and Genomics, Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, MG, Brasil.
- Laboratory of Energy Metabolism and Body Composition, Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, MG, Brasil.
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Martínez-Almoyna Rifá E, López González ÁA, Tárraga López PJ, Paublini H, Vallejos D, Ramírez Manent JI. [Relationship between diabesity and elevated values of metabolic-associated steatotic liver disease risk scales in Spanish workers using body mass index and the body adiposity estimator criteria of Clínica de Navarra]. NUTR HOSP 2025. [PMID: 40195779 DOI: 10.20960/nh.05441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/09/2025] Open
Abstract
INTRODUCTION diabesity (coexistence of diabetes and obesity) and metabolic associated steatotic liver disease (MASLD) are two very frequent pathologies whose prevalence is increasing every day. OBJECTIVE to find out how these two pathological entities are associated in a group of Spanish workers. METHODOLOGY a descriptive, cross-sectional study was carried out in 219477 workers to assess the association between diabesity (applying a double criterion, the body mass index BMI and the Clínica Universitaria de Navarra body adiposity estimator CUN BAE) and different risk scales for MASLD and liver fibrosis. RESULTS all MASH and liver fibrosis risk scales show higher values in people with diabesity applying the two criteria compared to people without diabesity. CONCLUSION diabesity and MASLD and liver fibrosis risk scales show a significant association in our study.
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Affiliation(s)
- Emilio Martínez-Almoyna Rifá
- Grupo ADEMA-SALUD. Institut Universitari d'Investigació en Ciències de la Salut (iUNICS). Facultad de Odontología. Escuela Universitaria-Universidad de las Islas Baleares - ADEMA-UIB
| | - Ángel Arturo López González
- Grupo ADEMA-SALUD. Institut Universitari d'Investigació en Ciències de la Salut (iUNICS). Facultad de Odontología. Escuela Universitaria-Universidad de las Islas Baleares - ADEMA-UIB
| | | | - Hernán Paublini
- Grupo ADEMA-SALUD. Institut Universitari d'Investigació en Ciències de la Salut (iUNICS). Facultad de Odontología. Escuela Universitaria-Universidad de las Islas Baleares - ADEMA-UIB
| | - Daniela Vallejos
- Grupo ADEMA-SALUD. Institut Universitari d'Investigació en Ciències de la Salut (iUNICS). Facultad de Odontología. Escuela Universitaria-Universidad de las Islas Baleares - ADEMA-UIB
| | - José Ignacio Ramírez Manent
- Grupo ADEMA-SALUD. Institut Universitari d'Investigació en Ciències de la Salut (iUNICS). Facultad de Odontología. Escuela Universitaria-Universidad de las Islas Baleares - ADEMA-UIB. Facultad de Medicina. Universidad de las Islas Baleares
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Tamini S, Bondesan A, Caroli D, Marazzi N, Sartorio A. The Ability of the Triglyceride-Glucose (TyG) Index and Modified TyG Indexes to Predict the Presence of Metabolic-Associated Fatty Liver Disease and Metabolic Syndrome in a Pediatric Population with Obesity. J Clin Med 2025; 14:2341. [PMID: 40217790 PMCID: PMC11989838 DOI: 10.3390/jcm14072341] [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: 03/10/2025] [Revised: 03/25/2025] [Accepted: 03/27/2025] [Indexed: 04/14/2025] Open
Abstract
Background: Metabolic-associated fatty liver disease (MASLD) and metabolic syndrome (MetS) are increasingly prevalent among children and adolescents with obesity, posing significant long-term metabolic and cardiovascular risks. Non-invasive identification of at-risk individuals is crucial for a timely intervention. This study aimed to evaluate the diagnostic performance of the triglyceride-glucose (TyG) index and its modified versions, TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC), in predicting MASLD and MetS in a large cohort of children and adolescents with obesity. Methods: A total of 758 children and adolescents with obesity (454 females, 304 males; mean age 14.8 ± 2.1 years; mean BMI 37.9 ± 6.2 kg/m2) were included. MASLD was diagnosed via ultrasonography, while MetS was defined using International Diabetes Federation criteria. TyG, TyG-WC, and TyG-BMI were calculated for all participants. Receiver operating characteristic (ROC) curves were generated to assess the diagnostic accuracy of these indexes, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: MASLD was detected in 38.9% of participants, with a higher prevalence in males (p < 0.0001). MetS was present in 27.8% of the cohort, with higher prevalence in males (p < 0.0001). Among the indexes, TyG-WC exhibited the highest sensitivity for MASLD (77.6%), whereas TyG-BMI had the highest specificity (63.3%). In predicting MetS, all three indexes performed better than for MASLD, with TyG demonstrating the highest PPV (54.5%) and TyG-BMI the highest NPV (87.5%). Predictive performance was lower in males than females, potentially due to sex-specific differences in fat distribution and metabolic response. Conclusions: TyG, TyG-WC, and TyG-BMI are promising, non-invasive tools for identifying children and adolescents with obesity at risk for MASLD and MetS. The superior sensitivity of TyG-WC and the high specificity of TyG-BMI highlight the value of incorporating anthropometric parameters into metabolic screening. Integrating these indexes into routine clinical practice may enhance early detection, allowing for timely intervention and personalized management strategies, ultimately reducing the long-term burden of metabolic and liver diseases in pediatric populations.
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Affiliation(s)
- Sofia Tamini
- Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Experimental Laboratory for Auxo-Endocrinological Research, 28824 Piancavallo-Verbania, Italy; (A.B.); (D.C.); (N.M.); (A.S.)
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48
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Zhou Y, Chen Y, Tang Y, Zhang S, Zhuang Z, Ni Q. Rising tide: the growing global burden and inequalities of early-onset type 2 diabetes among youths aged 15-34 years (1990-2021). Diabetol Metab Syndr 2025; 17:103. [PMID: 40140909 PMCID: PMC11948681 DOI: 10.1186/s13098-025-01673-0] [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: 11/19/2024] [Accepted: 03/16/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is increasingly affecting people aged 15-34, posing a serious public health challenge due to its faster progression and higher complication risks. This study examines the global, regional, and national burden of early-onset T2DM from 1990 to 2021, emphasizing trends and disparities across different sociodemographic contexts. METHODS Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, we analyzed incidence, prevalence, mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) in people aged 15-34. Stratifications included age, sex, and the Socio-Demographic Index (SDI). Joinpoint regression significant temporal shifts, and decomposition analysis attributed changes in T2DM burden to factors such as prevalence, population growth, aging, and case fatality rates. Inequality was assessed with the Slope Index of Inequality and Concentration Index. RESULTS From 1990 to 2021, early-onset T2DM incidence and prevalence rose significantly worldwide, especially in high-SDI regions. Although global mortality and DALYs appeared relatively stable, low-SDI regions showed worrisome increases. Rising T2DM prevalence was the principal driver of mortality and DALYs, notably in low- and middle-SDI regions. Inequality analyses indicated widening disparities, with higher incidence and prevalence in high-SDI countries and more severe outcomes in low-SDI countries. CONCLUSIONS The global burden of early-onset T2DM among youths is escalating, with significant disparities across different sociodemographic levels. The findings underscore the urgent need for targeted public health interventions. Future research should focus on the underlying factors driving these trends and explore strategies for effective prevention and management of early-onset T2DM.
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Affiliation(s)
- Yang Zhou
- Department of Endocrinology, Guang'Anmen Hospital of China Academy of Chinese Medical Sciences, Guang'anmen Hospital, Beixiange 5, Xicheng District, Beijing, 100053, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Yupeng Chen
- Department of Endocrinology, Guang'Anmen Hospital of China Academy of Chinese Medical Sciences, Guang'anmen Hospital, Beixiange 5, Xicheng District, Beijing, 100053, China
| | - Yiting Tang
- Beijing University of Chinese Medicine, Beijing, China
| | - Shan Zhang
- Department of Endocrinology, Guang'Anmen Hospital of China Academy of Chinese Medical Sciences, Guang'anmen Hospital, Beixiange 5, Xicheng District, Beijing, 100053, China
| | - Zifan Zhuang
- Department of Endocrinology, Guang'Anmen Hospital of China Academy of Chinese Medical Sciences, Guang'anmen Hospital, Beixiange 5, Xicheng District, Beijing, 100053, China
| | - Qing Ni
- Department of Endocrinology, Guang'Anmen Hospital of China Academy of Chinese Medical Sciences, Guang'anmen Hospital, Beixiange 5, Xicheng District, Beijing, 100053, China.
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Randeni N, Luo J, Xu B. Critical Review on Anti-Obesity Effects of Anthocyanins Through PI3K/Akt Signaling Pathways. Nutrients 2025; 17:1126. [PMID: 40218884 PMCID: PMC11990295 DOI: 10.3390/nu17071126] [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: 03/03/2025] [Revised: 03/18/2025] [Accepted: 03/23/2025] [Indexed: 04/14/2025] Open
Abstract
Obesity is a global health crisis and is one of the major reasons for the rising prevalence of metabolic disorders such as type 2 diabetes, cardiovascular diseases, and certain cancers. There has been growing interest in the search for natural molecules with potential anti-obesity effects; among the phytochemicals of interest are anthocyanins, which are flavonoid pigments present in many fruits and vegetables. Anthocyanins influence obesity via several signaling pathways. The PI3K/Akt signaling pathway plays a major role with a focus on downstream targets such as GLUT4, FOXO, GSK3β, and mTOR, which play a central role in the regulation of glucose metabolism, lipid storage, and adipogenesis. The influence of critical factors such as oxidative stress and inflammation also affect the pathophysiology of obesity. However, the studies reviewed have certain limitations, including variations in experimental models, bioavailability challenges, and a lack of extensive clinical validation. While anthocyanin shows tremendous potential, challenges such as poor bioavailability, stability, and regulatory matters must be overcome for successful functional food inclusion of anthocyanins. The future of anthocyanin-derived functional foods lies in their ability to overcome hurdles. Therefore, this review highlights the molecular mechanisms of obesity through the PI3K/Akt signaling pathways and explores how anthocyanins can modulate these signaling pathways to address obesity and related metabolic disorders. It also addresses some ways to solve the challenges, like bioavailability and stability, while emphasizing future possibilities for anthocyanin-based functional foods in obesity management.
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Affiliation(s)
| | | | - Baojun Xu
- Food Science and Technology Program, Department of Life Sciences, Beijing Normal-Hong Kong Baptist University, Zhuhai 519087, China; (N.R.); (J.L.)
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Kantapan J, Katsube T, Wang B. High-Fat Diet and Altered Radiation Response. BIOLOGY 2025; 14:324. [PMID: 40282189 PMCID: PMC12024794 DOI: 10.3390/biology14040324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/11/2025] [Accepted: 03/19/2025] [Indexed: 04/29/2025]
Abstract
High-fat diets (HFDs) have become increasingly prevalent in modern societies, driving rising rates of obesity and metabolic syndrome. Concurrently, radiation exposure from medical treatments and environmental sources poses health risks shaped by both biological and environmental factors. This review explores the intersection between HFDs and radiation sensitivity/susceptibility, focusing on how diet-induced metabolic alterations influence the body's response to radiation. Evidence from preclinical and clinical studies indicates that HFDs significantly alter metabolism, leading to increased oxidative stress and immune system dysregulation. These metabolic changes can exacerbate radiation-induced oxidative stress, inflammation, and DNA damage, potentially increasing radiation sensitivity in normal tissues. Conversely, obesity and HFD-induced metabolic disruptions may activate cellular pathways involved in DNA repair, cell survival, and inflammatory responses, fostering tumor resistance and modifying the tumor microenvironment, which may impair the efficacy of radiation therapy in cancer treatment. Understanding the interplay between diet and radiation exposure is critical for optimizing public health guidelines and improving therapeutic outcomes. These findings underscore the need for further research into dietary interventions that may mitigate radiation-associated risks.
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Affiliation(s)
- Jiraporn Kantapan
- Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Takanori Katsube
- Institute for Radiological Science, National Institutes for Quantum Science and Technology (QST), Chiba 263-8555, Japan;
| | - Bing Wang
- Institute for Radiological Science, National Institutes for Quantum Science and Technology (QST), Chiba 263-8555, Japan;
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