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Kumari S, Peela S, Srilatha M, Girish BP, Nagaraju GP. Adiponectin: its role in diabetic and pancreatic cancer. Mol Aspects Med 2025; 103:101370. [PMID: 40403652 DOI: 10.1016/j.mam.2025.101370] [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: 02/08/2025] [Revised: 04/24/2025] [Accepted: 05/18/2025] [Indexed: 05/24/2025]
Abstract
Adiponectin (ApN) is an antidiabetic and anti-inflammatory protein synthesized by adipose tissue. It is essential in regulating insulin sensitivity, glucose, and lipid metabolism by controlling AMPK, PPARα, and MAPK signals. It is an anti-inflammatory property that protects pancreatic β-cells. Often, low levels of ApN are linked to obesity, type II diabetes and the development of PDAC. However, changes in lifestyle and the use of certain drugs can improve ApN function and insulin sensitivity. PDAC is a highly aggressive cancer linked to obesity, type II diabetes, and insulin resistance. ApN plays a complex role in PDAC progression and can suppress PDAC development by weakening β-catenin signaling. Decreases in ApN levels are associated with increased PDAC risk in diabetic patients. PDAC and diabetes are interconnected through the development of insulin resistance, islet dysfunction, change in immunological response, inflammation, oxidative stress, and altered hormone secretion. Genetic studies highlight specific genes like HNF4G and PDX1 that influence both conditions and miRNAs such as miR-19a promote tumor progression through the PI3K/AKT pathway. This review discusses the role of ApN in diabetes and PDAC and the interrelation between diabetes and PDAC.
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Affiliation(s)
- Seema Kumari
- Department of Biotechnology, Dr.B.R. Ambedkar University, Srikakulam, 532410, AP, India
| | - Sujatha Peela
- Department of Biotechnology, Dr.B.R. Ambedkar University, Srikakulam, 532410, AP, India
| | - Mundla Srilatha
- Department of Biotechnology, Sri Venkateswara University, Tirupati, Andhra Pradesh, 517502, India
| | - Bala Prabhakar Girish
- Regional Agricultural Research Station, Institute of Frontier Technology, Acharya N G Ranga Agricultural University, Tirupati, India
| | - Ganji Purnachandra Nagaraju
- School of Medicine, Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
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Yu L, Yang YX, Gong Z, Wan Q, Du Y, Zhou Q, Xiao Y, Zahr T, Wang Z, Yu Z, Yang K, Geng J, Fried SK, Li J, Haeusler RA, Leong KW, Bai L, Wu Y, Sun L, Wang P, Zhu BT, Wang L, Qiang L. FcRn-dependent IgG accumulation in adipose tissue unmasks obesity pathophysiology. Cell Metab 2025; 37:656-672.e7. [PMID: 39674176 PMCID: PMC11885036 DOI: 10.1016/j.cmet.2024.11.001] [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: 02/14/2024] [Revised: 06/24/2024] [Accepted: 11/01/2024] [Indexed: 12/16/2024]
Abstract
Immunoglobulin G (IgG) is traditionally recognized as a plasma protein that neutralizes antigens for immune defense. However, our research demonstrates that IgG predominantly accumulates in adipose tissue during obesity development, triggering insulin resistance and macrophage infiltration. This accumulation is governed by neonatal Fc receptor (FcRn)-dependent recycling, orchestrated in adipose progenitor cells and macrophages during the early and late stages of diet-induced obesity (DIO), respectively. Targeting FcRn abolished IgG accumulation and rectified insulin resistance and metabolic degeneration in DIO. By integrating artificial intelligence (AI) modeling with in vivo and in vitro experimental models, we unexpectedly uncovered an interaction between IgG's Fc-CH3 domain and the insulin receptor's ectodomain. This interaction hinders insulin binding, consequently obstructing insulin signaling and adipocyte functions. These findings unveil adipose IgG accumulation as a driving force in obesity pathophysiology, providing a novel therapeutic strategy to tackle metabolic dysfunctions.
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Affiliation(s)
- Lexiang Yu
- Naomi Berrie Diabetes Center, Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Yong Xiao Yang
- Research Center for Endocrine and Metabolic Diseases, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, China
| | - Zhen Gong
- Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA
| | - Qianfen Wan
- Naomi Berrie Diabetes Center, Department of Medicine, Columbia University, New York, NY 10032, USA
| | - Yifei Du
- MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
| | - Qiuzhong Zhou
- Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore
| | - Yang Xiao
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
| | - Tarik Zahr
- Naomi Berrie Diabetes Center, Department of Medicine, Columbia University, New York, NY 10032, USA
| | - Zhaobin Wang
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Zhewei Yu
- Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Kangkang Yang
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Shandong Provincial Hospital, School of Laboratory Animal & Shandong Laboratory Animal Center, Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250021, China; Institute for Genome Engineered Animal Models of Human Diseases, College of Integrative Medicine, National Center of Genetically Engineered Animal Models for International Research, Liaoning Province Key Lab of Genetically Engineered Animal Models, Dalian Medical University, Dalian 116044, China
| | - Jinyang Geng
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Shandong Provincial Hospital, School of Laboratory Animal & Shandong Laboratory Animal Center, Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250021, China; Institute for Genome Engineered Animal Models of Human Diseases, College of Integrative Medicine, National Center of Genetically Engineered Animal Models for International Research, Liaoning Province Key Lab of Genetically Engineered Animal Models, Dalian Medical University, Dalian 116044, China
| | - Susan K Fried
- Diabetes Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jing Li
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Rebecca A Haeusler
- Naomi Berrie Diabetes Center, Department of Medicine, Columbia University, New York, NY 10032, USA
| | - Kam W Leong
- Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
| | - Lin Bai
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Yingjie Wu
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Shandong Provincial Hospital, School of Laboratory Animal & Shandong Laboratory Animal Center, Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250021, China; Institute for Genome Engineered Animal Models of Human Diseases, College of Integrative Medicine, National Center of Genetically Engineered Animal Models for International Research, Liaoning Province Key Lab of Genetically Engineered Animal Models, Dalian Medical University, Dalian 116044, China
| | - Lei Sun
- Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore
| | - Pan Wang
- Research Center for Endocrine and Metabolic Diseases, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, China
| | - Bao Ting Zhu
- Research Center for Endocrine and Metabolic Diseases, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, China
| | - Liheng Wang
- Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
| | - Li Qiang
- Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
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Vasileva F, Font-Lladó R, Carreras-Badosa G, Cazorla-González J, López-Bermejo A, Prats-Puig A. Integrated neuromuscular training intervention applied in schools induces a higher increase in salivary high molecular weight adiponectin and a more favorable body mass index, cardiorespiratory fitness and muscle strength in children as compared to the traditional physical education classes. Front Public Health 2024; 12:1337958. [PMID: 38756879 PMCID: PMC11096568 DOI: 10.3389/fpubh.2024.1337958] [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: 11/13/2023] [Accepted: 04/19/2024] [Indexed: 05/18/2024] Open
Abstract
Background High-molecular-weight adiponectin (HMW-adiponectin) is a cardio-metabolic health protector. Objectives: (1) to compare body mass index (BMI), cardiorespiratory fitness (CRF) and muscle strength (MS) in healthy school-children depending on their baseline salivary-HMW-adiponectin concentration; and (2) to apply a 3-month integrated neuromuscular training (INT) and evaluate its effects on salivary-HMW-adiponectin concentration, BMI, CRF and MS in the same children. Additional goal: to identify if any potential changes during the 3-month period may be related to a potential change in salivary-HMW-adiponectin concentration. Methods Ninety children (7.4 ± 0.3 years) were recruited in primary schools and randomly allocated into control or intervention group. The intervention consisted of a 3-month INT applied during physical education (PE) classes, twice-weekly, while the control group had traditional PE classes. Body mass and height were measured, BMI was calculated and HMW-adiponectin was quantified in saliva. To assess CRF and MS, 800 m-run and hand-dynamometry were applied, respectively. All measurements were performed twice, at baseline and after 3 months. Results Children with higher baseline salivary-HMW-adiponectin have more favorable BMI (p = 0.006) and slightly higher CRF (p = 0.017) in comparison to the children with lower baseline salivary-HMW-adiponectin. There were no big changes after the 3-month-period neither in the control, nor the INT group. However, it is worthy to note that the INT induced slightly higher increase in salivary-HMW-adiponectin (p = 0.007), and a slightly higher improvement in BMI (p = 0.028), CRF (p = 0.043) and MS (p = 0.003), as compared to the traditional PE classes. Finally, the INT-induced improvement in CRF was associated with the increased post-salivary-HMW-adiponectin concentration (p = 0.022). Conclusion Main findings may suggest the potential utility of an INT as a cost-effective strategy that can be applied in schools to induce cardio-protective effects in school-children.
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Affiliation(s)
- Fidanka Vasileva
- Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research, Girona, Spain
- University School of Health and Sport, University of Girona, Girona, Spain
| | - Raquel Font-Lladó
- University School of Health and Sport, University of Girona, Girona, Spain
- Research Group of Culture and Education, Institute of Educational Research, University of Girona, Girona, Spain
| | - Gemma Carreras-Badosa
- Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research, Girona, Spain
| | | | - Abel López-Bermejo
- Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research, Girona, Spain
- Department of Medical Sciences, University of Girona, Girona, Spain
- Pediatric Endocrinology, Dr. Josep Trueta Hospital, Girona, Spain
| | - Anna Prats-Puig
- University School of Health and Sport, University of Girona, Girona, Spain
- Research Group of Clinical Anatomy, Embryology and Neuroscience, Department of Medical Sciences, University of Girona, Girona, Spain
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Yao CB, Feng L, Wu P, Liu Y, Jiang J, Zhang L, Mi HF, Zhou XQ, Jiang WD. Promotion of fatty acid metabolism and glucose metabolism in the muscle of sub-adult grass carp ( Ctenopharyngodon idella): The role of alpha-linoleic acid/linoleic acid (ALA/LNA) ratios. Food Chem X 2023; 19:100752. [PMID: 37384144 PMCID: PMC10293787 DOI: 10.1016/j.fochx.2023.100752] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 05/31/2023] [Accepted: 06/09/2023] [Indexed: 06/30/2023] Open
Abstract
The n6/n3 ratios improved meat quality of terrestrial animals, but alpha-linolenic acid/linoleic acid (ALA/LNA) ratios were rarely studied in aquatic animals. In this study, sub-adult grass carp (Ctenopharyngodon idella) were fed diets fed diets containing six varying ALA/LNA ratios (0.03, 0.47, 0.92, 1.33, 1.69, and 2.15) for 9 weeks and the total value of n3 + n6 (1.98) was kept constant for all six treatments. The results indicated optimal ALA/LNA ratio improved growth performance, changed fatty acid composition in grass carp muscle, and promoted glucose metabolism. Additionally, optimal ALA/LNA ratio improved chemical attributes by increasing crude protein and lipid contents, and technological attributes by increasing pH24h value and shear force in grass carp muscle. The signaling pathways related to fatty acid metabolism and glucose metabolism (LXRα/SREBP-1, PPARα, PPARγ, AMPK) might be responsible for these changes. Dietary optimal ALA/LNA ratio based on PWG, UFA and glucose contents was 1.03, 0.88 and 0.92, respectively.
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Affiliation(s)
- Chi-Bei Yao
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
| | - Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
- Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Sichuan 611130, China
| | - Pei Wu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
- Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Sichuan 611130, China
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
- Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Sichuan 611130, China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
| | - Lu Zhang
- Tongwei Co., Ltd., Chengdu, China
- Healthy Aquaculture Key Laboratory of Sichuan Province, Sichuan 610041, China
| | | | - Xiao-Qiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
- Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Sichuan 611130, China
| | - Wei-Dan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
- Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
- Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Sichuan 611130, China
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Chong HW, Son J, Chae C, Jae C. The relationship between skeletal muscle mass and the KOSHA cardiovascular risk in obese male workers. Ann Occup Environ Med 2023; 35:e40. [PMID: 38029272 PMCID: PMC10654537 DOI: 10.35371/aoem.2023.35.e40] [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: 07/20/2023] [Revised: 09/08/2023] [Accepted: 09/17/2023] [Indexed: 12/01/2023] Open
Abstract
Background Efforts for the prevention and management of cardiovascular diseases (CVDs) in workers have been actively pursued. Obesity is one of the important risk factors related to CVDs. Obesity has various metabolic characteristics, and some individuals can be metabolically healthy. Body composition including skeletal muscle mass is known to have protective effect in obesity. The study aims to investigate the association between skeletal muscle mass and Korea Occupational Safety and Health Agency (KOSHA) CVD risk among obese male manufacturing workers in Korea and to identify appropriate indicators of skeletal muscle mass for predicting risk of CVDs. Methods The study was conducted on 2,007 obese male workers at a manufacturing industry aged more than 19 years. Skeletal muscle mass, skeletal muscle index (SMI), skeletal muscle mass percent (SMM%) and skeletal muscle to body fat ratio (MFR) were used to evaluate body composition and these indicators were divided into quartiles. The odds ratios (ORs) and 95% confidence intervals (CIs) for the KOSHA CVD risk groups according to quartiles of skeletal muscle mass indicators were estimated using ordinal logistic regression analysis. Results The OR for the KOSHA CVD risk groups in the highest quartile of SMI was 1.67 (95% CI: 1.42-1.92), while the ORs for the KOSHA CVD risk groups in the highest quartiles of SMM%, SMM/body mass index (BMI), and MFR were 0.47 (95% CI: 0.22-0.72), 0.51 (95% CI: 0.05-0.76), and 0.48 (95% CI: 0.23-0.74), respectively. Conclusions We found that high SMI increase the likelihood of high risk of CVDs, while high SMM%, SMM/BMI, and MFR lower the likelihood of high risk of CVDs. Accurate evaluation of skeletal muscle mass can help assess the cardiovascular risk in obese male workers.
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Affiliation(s)
- Hyo Won Chong
- Department of Occupational and Environmental Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - JunSeok Son
- Department of Occupational and Environmental Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Changho Chae
- Department of Occupational and Environmental Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Changho Jae
- Department of Occupational and Environmental Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
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Delgado-Bravo M, Hart DA, Reimer RA, Herzog W. Alterations in skeletal muscle morphology and mechanics in juvenile male Sprague Dawley rats exposed to a high-fat high-sucrose diet. Sci Rep 2023; 13:12013. [PMID: 37491416 PMCID: PMC10368627 DOI: 10.1038/s41598-023-38487-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 07/09/2023] [Indexed: 07/27/2023] Open
Abstract
Although once a health concern largely considered in adults, the obesity epidemic is now prevalent in pediatric populations. While detrimental effects on skeletal muscle function have been seen in adulthood, the effects of obesity on skeletal muscle function in childhood is not clearly understood. The purpose of this study was to determine if the consumption of a high-fat high-sucrose (HFS) diet, starting in the post-weaning period, leads to changes in skeletal muscle morphology and mechanics after 14 weeks on the HFS diet. Eighteen 3-week-old male CD-Sprague Dawley rats were randomly assigned to a HFS (C-HFS, n = 10) or standard chow diet (C-CHOW, n = 8). Outcome measures included: weekly energy intake, activity levels, oxygen consumption, body mass, body composition, metabolic profile, serum protein levels, and medial gastrocnemius gene expression, morphology, and mechanics. The main findings from this study were that C-HFS rats: (1) had a greater body mass and percent body fat than control rats; (2) showed early signs of metabolic syndrome; (3) demonstrated potential impairment in muscle remodeling; (4) produced lower relative muscle force; and (5) had a shift in the force-length relationship, indicating that the medial gastrocnemius had shorter muscle fiber lengths compared to those of C-CHOW rats. Based on the results of this study, we conclude that exposure to a HFS diet led to increased body mass, body fat percentage, and early signs of metabolic syndrome, resulting in functional deficits in MG of childhood rats.
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Affiliation(s)
- Mauricio Delgado-Bravo
- Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada
- Carrera de Kinesiología, Departamento de Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - David A Hart
- Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada
- McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada
- Department of Surgery, University of Calgary, Calgary, AB, Canada
| | - Raylene A Reimer
- Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada
- Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada
| | - Walter Herzog
- Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada.
- McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada.
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Queiroz TS, Allebrandt Neto EW, Santos MP, Correia FS, Magalhães DA, Buzelle SL, Pereira MP, França SA, Kawashita NH. Effects of a low-protein, high-carbohydrate diet administered after weaning and the reversal of that diet in adult rats. AN ACAD BRAS CIENC 2023; 95:e20220436. [PMID: 37436230 DOI: 10.1590/0001-3765202320220436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 11/08/2022] [Indexed: 07/13/2023] Open
Abstract
To evaluate the effects in adults rats submitted of a low-protein, high-carbohydrate (LPHC; 6% protein, 74% carbohydrate) diet and reversion (R) to a balanced diet introduced after weaning. Research methods & procedures: Male rats weigting approximately 100g (30 to 32 d old) were treated with control (C; 17% protein, 63% carbohydrate) or LPHC diets for 120 days. The reverse group (R) was treated with the LPHC diet for 15 days, and changed to C diet for another 105 days. Results: The LPHC group showed an increase in serum fasting triglycerides (TAG). Serum adiponectin was increased only in the LPHC group. Lipoprotein lipase (LPL) activity was decreased in the extensor digitorum longus (EDL) and cardiac muscles. The adiponectin receptor 1 content is the same among groups in the cardiac muscle, but it is lower in the EDL muscle in the LPHC group. In animals from the R group, these parameters are the same as the LPHC group. Thus, the LPHC diet administered for a long period, it promotes an increase in TAG. It is possible that there is adiponectin resistance in the EDL muscle, due to the lower LPL activity. The reversal of the LPHC diet did not normalize these parameters.
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Affiliation(s)
- Thaís S Queiroz
- Universidade Federal de Mato Grosso, Departmento de Química, Av. Fernando Correa da Costa, 2367, 78060-900 Cuiabá, MT, Brazil
| | - Edgar W Allebrandt Neto
- Universidade Federal de Mato Grosso, Departmento de Química, Av. Fernando Correa da Costa, 2367, 78060-900 Cuiabá, MT, Brazil
| | - Maísa P Santos
- Universidade Federal de Mato Grosso, Departmento de Química, Av. Fernando Correa da Costa, 2367, 78060-900 Cuiabá, MT, Brazil
| | - Francyele S Correia
- Universidade Federal de Mato Grosso, Departmento de Química, Av. Fernando Correa da Costa, 2367, 78060-900 Cuiabá, MT, Brazil
| | - Diego A Magalhães
- Universidade Federal de Mato Grosso, Departmento de Química, Av. Fernando Correa da Costa, 2367, 78060-900 Cuiabá, MT, Brazil
| | - Samyra L Buzelle
- Universidade de Várzea Grande, Av. Dom Orlando Chaves, 2655, 78118-900 Várzea Grande, MT, Brazil
| | - Mayara P Pereira
- Universidade Federal de Mato Grosso, Departmento de Química, Av. Fernando Correa da Costa, 2367, 78060-900 Cuiabá, MT, Brazil
| | - Suelém A França
- Universidade Federal de Mato Grosso, Departmento de Química, Av. Fernando Correa da Costa, 2367, 78060-900 Cuiabá, MT, Brazil
| | - Nair H Kawashita
- Universidade Federal de Mato Grosso, Departmento de Química, Av. Fernando Correa da Costa, 2367, 78060-900 Cuiabá, MT, Brazil
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Abdalla MMI, Mohanraj J, Somanath SD. Adiponectin as a therapeutic target for diabetic foot ulcer. World J Diabetes 2023; 14:758-782. [PMID: 37383591 PMCID: PMC10294063 DOI: 10.4239/wjd.v14.i6.758] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/25/2023] [Accepted: 04/24/2023] [Indexed: 06/14/2023] Open
Abstract
The global burden of diabetic foot ulcers (DFUs) is a significant public health concern, affecting millions of people worldwide. These wounds cause considerable suffering and have a high economic cost. Therefore, there is a need for effective strategies to prevent and treat DFUs. One promising therapeutic approach is the use of adiponectin, a hormone primarily produced and secreted by adipose tissue. Adiponectin has demonstrated anti-inflammatory and anti-atherogenic properties, and researchers have suggested its potential therapeutic applications in the treatment of DFUs. Studies have indicated that adiponectin can inhibit the production of pro-inflammatory cytokines, increase the production of vascular endothelial growth factor, a key mediator of angiogenesis, and inhibit the activation of the intrinsic apoptotic pathway. Additionally, adiponectin has been found to possess antioxidant properties and impact glucose metabolism, the immune system, extracellular matrix remodeling, and nerve function. The objective of this review is to summarize the current state of research on the potential role of adiponectin in the treatment of DFUs and to identify areas where further research is needed in order to fully understand the effects of adiponectin on DFUs and to establish its safety and efficacy as a treatment for DFUs in the clinical setting. This will provide a deeper understanding of the underlying mechanisms of DFUs that can aid in the development of new and more effective treatment strategies.
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Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Physiology, Human Biology Division, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Jaiprakash Mohanraj
- Department of Biochemistry, Human Biology Division, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Sushela Devi Somanath
- Department of Microbiology, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
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Zhao Y, Zhao W, Bu H, Toshiyoshi M, Zhao Y. Liraglutide on type 2 diabetes mellitus with nonalcoholic fatty liver disease: A systematic review and meta-analysis of 16 RCTs. Medicine (Baltimore) 2023; 102:e32892. [PMID: 36820578 PMCID: PMC9907937 DOI: 10.1097/md.0000000000032892] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/12/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of type 2 diabetes mellitus (T2DM). Our aim is to investigate the effects of liraglutide on T2DM with NAFLD. METHODS Relevant articles published from the earliest publication to March 2022 were selected from several databases. The Cochrane Collaboration's RevMan software was used for the analysis. RESULTS Sixteen studies are selected for this meta-analysis, which includes totally 634 patients in the treatment group and 630 patients in the control group. As a result, 14 studies show that fasting plasma glucose levels of the experimental group are lower than that of the control group; 15 studies show that glycosylated hemoglobin A1c levels of the experimental group are lower than that of the control group; 13 studies show that triglyceride levels of the experimental group are lower than that of the control group; twelve studies show that total cholesterol levels of the experimental group are lower than that of the control group; 10 studies show that alanine aminotransferase levels of the experimental group is lower than that of the control group; 10 studies show that no significant difference in changes in aspartate transaminase between 2 groups; 13 studies show that low density lipoprotein cholesterol levels of the experimental group is lower than that of the control group; 9 studies show that no significant difference in changes in high density lipoprotein cholesterol between 2 groups; 7 studies mentioned adverse effects and the difference is significant. CONCLUSION Liraglutide is potentially curative for T2DM with NAFLD.
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Affiliation(s)
- Yan Zhao
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Wenli Zhao
- Department of Public Health, International College, Krirk University, Bangkok, Thailand
- Liver Center, Saga University Hospital, Saga University, Saga, Japan
| | - Huaien Bu
- School of Health Science and Engineering, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Maeda Toshiyoshi
- International Education College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ye Zhao
- Department of Public Health, International College, Krirk University, Bangkok, Thailand
- * Correspondence: Ye Zhao, Department of Public Health, International College, Krirk University, Bangkok 10220, Thailand (e-mail: )
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Samaha MM, Helal MG, El-Sherbiny M, Said E, Salem HA. Indapamide Increases IRS1 Expression and Modifies Adiponectin/NLRP3/PPARγ Crosstalk in Type 2 Diabetic Rats. Antioxidants (Basel) 2022; 11:antiox11040691. [PMID: 35453376 PMCID: PMC9026493 DOI: 10.3390/antiox11040691] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 03/27/2022] [Accepted: 03/29/2022] [Indexed: 02/01/2023] Open
Abstract
The current study aimed to evaluate the anti-diabetic effects of canagliflozin (CANA) and indapamide (INDA) and their impacts as adiponectin modulators in experimentally induced type 2 diabetes mellitus (T2DM). T2DM was associated with a significant rise in blood glucose level and HbA1C%, andreduced adiponectin and insulin secretions. Moreover, the malondialdehyde (MDA) contents in both the epididymal adipocytes and soleus muscle significantly escalated, while the total antioxidant capacity (TAC) and epididymal adipocyte Nrf2 expression significantly declined. Moreover, serum TNF-α, epididymal adipocyte’s NOD-like receptor protein 3, NLRP3, NF-κB and CD68 expressions markedly escalated, and serum IL-10 significantly declined. Furthermore, there was a significant escalation in PPARγ expression in epididymal adipocytes, with a significant reduction in soleus muscle’s expression of IRS1. CANA and INDA treatments markedly reduced blood glucose levels, increased adiponectin and insulin secretion, enhanced anti-oxidant defenses, and reduced oxidative burden, with marked anti-inflammatory impact. Interestingly, the impact of indapamide on DM indices and oxidative and inflammatory changes was comparable to that of canagliflozin. Nevertheless, indapamide had a superior effect compared to canagliflozin on HbA1c%, expression of IRS1 and reduction of NF-κB and CD68 expressions. INDA could be effective in regulating T2DM, with underlined anti-diabetic, antioxidant, and anti-inflammatory properties. INDA increased IRS1 expression and modified adiponectin/NLRP3/PPARγ crosstalk. The impacts of INDA are comparable to those of the standard anti-diabetic drug CANA.
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Affiliation(s)
- Mahmoud M. Samaha
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.G.H.); (H.A.S.)
| | - Manar G. Helal
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.G.H.); (H.A.S.)
| | - Mohamed El-Sherbiny
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh P.O. Box 71666, Saudi Arabia;
- Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Eman Said
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.G.H.); (H.A.S.)
- Faculty of Pharmacy, New Mansoura University, New Mansoura 7723730, Egypt
- Correspondence:
| | - Hatem A. Salem
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; (M.M.S.); (M.G.H.); (H.A.S.)
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11
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Park JS, Saeed K, Jo MH, Kim MW, Lee HJ, Park CB, Lee G, Kim MO. LDHB Deficiency Promotes Mitochondrial Dysfunction Mediated Oxidative Stress and Neurodegeneration in Adult Mouse Brain. Antioxidants (Basel) 2022; 11:antiox11020261. [PMID: 35204143 PMCID: PMC8868245 DOI: 10.3390/antiox11020261] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 01/27/2022] [Indexed: 11/17/2022] Open
Abstract
Age-related decline in mitochondrial function and oxidative stress plays a critical role in neurodegeneration. Lactate dehydrogenase-B (LDHB) is a glycolytic enzyme that catalyzes the conversion of lactate, an important brain energy substrate, into pyruvate. It has been reported that the LDHB pattern changes in the brain during ageing. Yet very little is known about the effect of LDHB deficiency on brain pathology. Here, we have used Ldhb knockout (Ldhb−/−) mice to test the hypothesis that LDHB deficiency plays an important role in oxidative stress-mediated neuroinflammation and neurodegeneration. LDHB knockout (Ldhb−/−) mice were generated by the ablation of the Ldhb gene using the Cre/loxP-recombination system in the C57BL/6 genetic background. The Ldhb−/− mice were treated with either osmotin (15 μg/g of the body; intraperitoneally) or vehicle twice a week for 5-weeks. After behavior assessments, the mice were sacrificed, and the cortical and hippocampal brain regions were analyzed through biochemical and morphological analysis. Ldhb−/− mice displayed enhanced reactive oxygen species (ROS) and lipid peroxidation (LPO) production, and they revealed depleted stores of cellular ATP, GSH:GSSG enzyme ratio, and downregulated expression of Nrf2 and HO-1 proteins, when compared to WT littermates. Importantly, the Ldhb−/− mice showed upregulated expression of apoptosis mediators (Bax, Cytochrome C, and caspase-3), and revealed impaired p-AMPK/SIRT1/PGC-1alpha signaling. Moreover, LDHB deficiency-induced gliosis increased the production of inflammatory mediators (TNF-α, Nf-ĸB, and NOS2), and revealed cognitive deficits. Treatment with osmotin, an adipoR1 natural agonist, significantly increased cellular ATP production by increasing mitochondrial function and attenuated oxidative stress, neuroinflammation, and neuronal apoptosis, probably, by upregulating p-AMPK/SIRT1/PGC-1alpha signaling in Ldhb−/− mice. In brief, LDHB deficiency may lead to brain oxidative stress-mediated progression of neurodegeneration via regulating p-AMPK/SIRT1/PGC-1alpha signaling, while osmotin could improve mitochondrial functions, abrogate oxidative stress and alleviate neuroinflammation and neurodegeneration in adult Ldhb−/− mice.
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Affiliation(s)
- Jun Sung Park
- Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea; (J.S.P.); (K.S.); (M.H.J.); (M.W.K.); (H.J.L.)
| | - Kamran Saeed
- Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea; (J.S.P.); (K.S.); (M.H.J.); (M.W.K.); (H.J.L.)
| | - Myeung Hoon Jo
- Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea; (J.S.P.); (K.S.); (M.H.J.); (M.W.K.); (H.J.L.)
| | - Min Woo Kim
- Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea; (J.S.P.); (K.S.); (M.H.J.); (M.W.K.); (H.J.L.)
| | - Hyeon Jin Lee
- Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea; (J.S.P.); (K.S.); (M.H.J.); (M.W.K.); (H.J.L.)
| | - Chan-Bae Park
- Department of Otolaryngology, Ajou University School of Medicine, Suwon 16499, Korea; or
| | - Gwang Lee
- Department of Physiology, Ajou University School of Medicine, Suwon 16499, Korea;
| | - Myeong Ok Kim
- Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea; (J.S.P.); (K.S.); (M.H.J.); (M.W.K.); (H.J.L.)
- Alz-Dementia Korea Co., Jinju 52828, Korea
- Correspondence: ; Tel.: +82-55-772-1345; Fax: +82-55-772-2656
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12
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Cai J, Hu Q, Lin H, Zhao J, Jiao H, Wang X. Adiponectin/adiponectin receptors mRNA expression profiles in chickens and their response to feed restriction. Poult Sci 2021; 100:101480. [PMID: 34700095 PMCID: PMC8554277 DOI: 10.1016/j.psj.2021.101480] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 09/06/2021] [Accepted: 09/13/2021] [Indexed: 11/08/2022] Open
Abstract
Adiponectin (ADPN) is related to fatty acid synthesis and oxidation in mammals. In chickens, the lipid metabolism, structure and sequence of ADPN are different from that in mammals. The aim of this study was to determine the role of ADPN in broilers lipid metabolism by investigating the temporal and spatial expression profiles of ADPN and its receptors, as well as their response to feed restriction. The results showed that the abdominal fat has the highest expression level, followed by the duodenum, glandular stomach, heart, hypothalamus, liver, and skeletal muscle. Broilers have high energy mobilization during their early stage of growth, in which the fat demand in the liver and muscles is high, thus the expression of ADPN and its receptor are also increased. To study the effects of feed restriction on ADPN and lipid metabolism, broilers were fasted for 12 h and refeed for 2 h. The results showed that fasting decreased the concentration of triglyceride (TG) (P < 0.05) and total cholesterol (TCHO) (P < 0.05) in plasma. The mRNA expression of ADPN in the liver (P < 0.05), breast (P < 0.05) and thigh (P < 0.05), and the mRNA expression of ADPNR1 in the liver (P < 0.05) and duodenum (P < 0.05) were significantly increased in the Fasted group. All above phenomena were recovered after refeeding, suggesting that feed restriction may promote the utilization of fatty acids in active metabolism tissues through ADPN, to guarantee the energy homeostasis of the body. However, the AMP-activated protein kinase (AMPK) signaling pathway and hepatic lipid metabolism were not necessary to cause the above changes under this experimental condition.
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Affiliation(s)
- Jiangxue Cai
- Department of Animal Science & Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong, 271018, P. R. China
| | - Qingmei Hu
- Department of Animal Science & Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong, 271018, P. R. China
| | - Hai Lin
- Department of Animal Science & Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong, 271018, P. R. China
| | - Jingpeng Zhao
- Department of Animal Science & Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong, 271018, P. R. China
| | - Hongchao Jiao
- Department of Animal Science & Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong, 271018, P. R. China
| | - Xiaojuan Wang
- Department of Animal Science & Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong, 271018, P. R. China.
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Correa‐da‐Silva F, Fliers E, Swaab DF, Yi C. Hypothalamic neuropeptides and neurocircuitries in Prader Willi syndrome. J Neuroendocrinol 2021; 33:e12994. [PMID: 34156126 PMCID: PMC8365683 DOI: 10.1111/jne.12994] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 04/19/2021] [Accepted: 05/04/2021] [Indexed: 02/06/2023]
Abstract
Prader-Willi Syndrome (PWS) is a rare and incurable congenital neurodevelopmental disorder, resulting from the absence of expression of a group of genes on the paternally acquired chromosome 15q11-q13. Phenotypical characteristics of PWS include infantile hypotonia, short stature, incomplete pubertal development, hyperphagia and morbid obesity. Hypothalamic dysfunction in controlling body weight and food intake is a hallmark of PWS. Neuroimaging studies have demonstrated that PWS subjects have abnormal neurocircuitry engaged in the hedonic and physiological control of feeding behavior. This is translated into diminished production of hypothalamic effector peptides which are responsible for the coordination of energy homeostasis and satiety. So far, studies with animal models for PWS and with human post-mortem hypothalamic specimens demonstrated changes particularly in the infundibular and the paraventricular nuclei of the hypothalamus, both in orexigenic and anorexigenic neural populations. Moreover, many PWS patients have a severe endocrine dysfunction, e.g. central hypogonadism and/or growth hormone deficiency, which may contribute to the development of increased fat mass, especially if left untreated. Additionally, the role of non-neuronal cells, such as astrocytes and microglia in the hypothalamic dysregulation in PWS is yet to be determined. Notably, microglial activation is persistently present in non-genetic obesity. To what extent microglia, and other glial cells, are affected in PWS is poorly understood. The elucidation of the hypothalamic dysfunction in PWS could prove to be a key feature of rational therapeutic management in this syndrome. This review aims to examine the evidence for hypothalamic dysfunction, both at the neuropeptidergic and circuitry levels, and its correlation with the pathophysiology of PWS.
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Affiliation(s)
- Felipe Correa‐da‐Silva
- Department of Endocrinology and MetabolismAmsterdam Gastroenterology Endocrinology and MetabolismAmsterdam University Medical Center (UMC)University of AmsterdamAmsterdamThe Netherlands
- Laboratory of EndocrinologyAmsterdam University Medical Center (UMC)University of AmsterdamAmsterdamThe Netherlands
- Department of Neuropsychiatric DisordersNetherlands Institute for NeuroscienceAn Institute of the Royal Netherlands Academy of Arts and SciencesAmsterdamThe Netherlands
| | - Eric Fliers
- Department of Endocrinology and MetabolismAmsterdam Gastroenterology Endocrinology and MetabolismAmsterdam University Medical Center (UMC)University of AmsterdamAmsterdamThe Netherlands
| | - Dick F. Swaab
- Department of Neuropsychiatric DisordersNetherlands Institute for NeuroscienceAn Institute of the Royal Netherlands Academy of Arts and SciencesAmsterdamThe Netherlands
| | - Chun‐Xia Yi
- Department of Endocrinology and MetabolismAmsterdam Gastroenterology Endocrinology and MetabolismAmsterdam University Medical Center (UMC)University of AmsterdamAmsterdamThe Netherlands
- Laboratory of EndocrinologyAmsterdam University Medical Center (UMC)University of AmsterdamAmsterdamThe Netherlands
- Department of Neuropsychiatric DisordersNetherlands Institute for NeuroscienceAn Institute of the Royal Netherlands Academy of Arts and SciencesAmsterdamThe Netherlands
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14
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Piccotti F, Rybinska I, Scoccia E, Morasso C, Ricciardi A, Signati L, Triulzi T, Corsi F, Truffi M. Lipofilling in Breast Oncological Surgery: A Safe Opportunity or Risk for Cancer Recurrence? Int J Mol Sci 2021; 22:ijms22073737. [PMID: 33916703 PMCID: PMC8038405 DOI: 10.3390/ijms22073737] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 03/30/2021] [Accepted: 03/31/2021] [Indexed: 02/08/2023] Open
Abstract
Lipofilling (LF) is a largely employed technique in reconstructive and esthetic breast surgery. Over the years, it has demonstrated to be extremely useful for treatment of soft tissue defects after demolitive or conservative breast cancer surgery and different procedures have been developed to improve the survival of transplanted fat graft. The regenerative potential of LF is attributed to the multipotent stem cells found in large quantity in adipose tissue. However, a growing body of pre-clinical evidence shows that adipocytes and adipose-derived stromal cells may have pro-tumorigenic potential. Despite no clear indication from clinical studies has demonstrated an increased risk of cancer recurrence upon LF, these observations challenge the oncologic safety of the procedure. This review aims to provide an updated overview of both the clinical and the pre-clinical indications to the suitability and safety of LF in breast oncological surgery. Cellular and molecular players in the crosstalk between adipose tissue and cancer are described, and heterogeneous contradictory results are discussed, highlighting that important issues still remain to be solved to get a clear understanding of LF safety in breast cancer patients.
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Affiliation(s)
- Francesca Piccotti
- Laboratorio di Nanomedicina ed Imaging Molecolare, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy; (F.P.); (C.M.); (A.R.)
| | - Ilona Rybinska
- Molecular Targeting Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (I.R.); (T.T.)
| | - Elisabetta Scoccia
- Breast Unit, Surgery Department, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy; (E.S.); (F.C.)
| | - Carlo Morasso
- Laboratorio di Nanomedicina ed Imaging Molecolare, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy; (F.P.); (C.M.); (A.R.)
| | - Alessandra Ricciardi
- Laboratorio di Nanomedicina ed Imaging Molecolare, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy; (F.P.); (C.M.); (A.R.)
| | - Lorena Signati
- Dipartimento di Scienze Biomediche e Cliniche “L. Sacco”, Università Degli Studi di Milano, 20157 Milano, Italy;
| | - Tiziana Triulzi
- Molecular Targeting Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (I.R.); (T.T.)
| | - Fabio Corsi
- Breast Unit, Surgery Department, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy; (E.S.); (F.C.)
- Dipartimento di Scienze Biomediche e Cliniche “L. Sacco”, Università Degli Studi di Milano, 20157 Milano, Italy;
| | - Marta Truffi
- Laboratorio di Nanomedicina ed Imaging Molecolare, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy; (F.P.); (C.M.); (A.R.)
- Correspondence: ; Tel.: +39-0382-592219
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Das S, Chattopadhyay D, Chatterjee SK, Mondal SA, Majumdar SS, Mukhopadhyay S, Saha N, Velayutham R, Bhattacharya S, Mukherjee S. Increase in PPARγ inhibitory phosphorylation by Fetuin-A through the activation of Ras-MEK-ERK pathway causes insulin resistance. Biochim Biophys Acta Mol Basis Dis 2020; 1867:166050. [PMID: 33359696 DOI: 10.1016/j.bbadis.2020.166050] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 11/13/2020] [Accepted: 12/14/2020] [Indexed: 12/20/2022]
Abstract
Obesity induced insulin resistance is primarily regulated by the inhibitory phosphorylation of peroxisome proliferator-activated receptor γ at serine 273 (PPARγS273) which has been shown to be regulated by MEK and ERK. An upstream regulatory molecule of this pathway could be a therapeutic option. Here we analyzed the involvement of Fetuin-A (FetA), a key hepato-adipokine implicated in insulin resistance, as an upstream regulator molecule for the regulation of PPARγ inhibitory phosphorylation. Mice fed with standard diet (SD), high fat diet (HFD) and HFD with FetA knockdown (HFD-FetAKD) were used to examine the role of FetA on PPARγS273 phosphorylation in adipocytes. The mechanism of regulation and its effect on skeletal muscle were studied using primary adipocytes, 3T3-L1 (preadipocyte) and C2C12 (myotube) cell lines. Increased FetA in HFD mice strongly correlated with augmentation of PPARγS273 phosphorylation in inflamed adipocytes while knockdown of FetA suppressed it. This effect of FetA was mediated through the activation of Ras which in turn activated MEK and ERK. On addressing how FetA could stimulate activation of Ras, we found that FetA triggered TNFα in inflamed adipocytes which induced Ras activation. The ensuing sharp fall in adiponectin level attenuated AMPK activation in skeletal muscle cells affecting mitochondrial ATP production. Our data reveal the essential role of FetA induced activation of Ras in regulating PPARγ inhibitory phosphorylation through Ras-MEK-ERK pathway which downregulates adiponectin disrupting skeletal muscle mitochondrial bioenergetics. Thus, FetA mediated PPARγ inactivation has adverse consequences upon adipocyte-myocyte crosstalk leading to disruption of energy homeostasis and loss of insulin sensitivity.
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Affiliation(s)
- Snehasis Das
- Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana (Institute of Science), Visva-Bharati (A Central University), Santiniketan - 731235, India
| | - Dipanjan Chattopadhyay
- Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana (Institute of Science), Visva-Bharati (A Central University), Santiniketan - 731235, India
| | - Subhendu K Chatterjee
- Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana (Institute of Science), Visva-Bharati (A Central University), Santiniketan - 731235, India
| | - Samim Ali Mondal
- Department of Endocrinology & Metabolism, Institute of Post-Graduate Medical Education & Research-Seth Sukhlal Karnani Memorial (IPGME&R-SSKM) Hospital, Kolkata 700025, India
| | | | - Satinath Mukhopadhyay
- Department of Endocrinology & Metabolism, Institute of Post-Graduate Medical Education & Research-Seth Sukhlal Karnani Memorial (IPGME&R-SSKM) Hospital, Kolkata 700025, India
| | - Nirmalendu Saha
- Department of Zoology, North-Eastern Hill University, Shillong 793022, India
| | | | - Samir Bhattacharya
- Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana (Institute of Science), Visva-Bharati (A Central University), Santiniketan - 731235, India
| | - Sutapa Mukherjee
- Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana (Institute of Science), Visva-Bharati (A Central University), Santiniketan - 731235, India.
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Dysregulated Autophagy Mediates Sarcopenic Obesity and Its Complications via AMPK and PGC1α Signaling Pathways: Potential Involvement of Gut Dysbiosis as a Pathological Link. Int J Mol Sci 2020; 21:ijms21186887. [PMID: 32961822 PMCID: PMC7555990 DOI: 10.3390/ijms21186887] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 09/17/2020] [Accepted: 09/18/2020] [Indexed: 12/13/2022] Open
Abstract
Sarcopenic obesity (SOB), which is closely related to being elderly as a feature of aging, is recently gaining attention because it is associated with many other age-related diseases that present as altered intercellular communication, dysregulated nutrient sensing, and mitochondrial dysfunction. Along with insulin resistance and inflammation as the core pathogenesis of SOB, autophagy has recently gained attention as a significant mechanism of muscle aging in SOB. Known as important cellular metabolic regulators, the AMP-activated protein kinase (AMPK) and the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) signaling pathways play an important role in autophagy, inflammation, and insulin resistance, as well as mutual communication between skeletal muscle, adipose tissue, and the liver. Furthermore, AMPK and PGC-1α signaling pathways are implicated in the gut microbiome-muscle axis. In this review, we describe the pathological link between SOB and its associated complications such as metabolic, cardiovascular, and liver disease, falls and fractures, osteoarthritis, pulmonary disease, and mental health via dysregulated autophagy controlled by AMPK and/or PGC-1α signaling pathways. Here, we propose potential treatments for SOB by modulating autophagy activity and gut dysbiosis based on plausible pathological links.
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Ergören MC, Söyler G, Sah H, Becer E. Investigation of potential genomic biomarkers for obesity and personalized medicine. Int J Biol Macromol 2018; 122:493-498. [PMID: 30416093 DOI: 10.1016/j.ijbiomac.2018.10.059] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 10/05/2018] [Accepted: 10/14/2018] [Indexed: 12/11/2022]
Abstract
Obesity, as a global health issue, is a complex metabolic syndrome and its association with many chronic diseases. The pathology of obesity results from an interaction of psychological, environmental and variety of genetic factors. Etiologic determinants and molecular pathophysiology of obesity have not yet understood clearly. Previously shown that genetic markers have a significant role in the development of obesity, although results are divergent with populations. Turkish Cypriots have a unique mixture of allele distributions as being a small-islander population. Therefore, the current study was aimed to evaluate the association between obesity and three putative obesity-related ADIPOQ, FTO and ACE gene markers, respectively. We investigated a possible association of ADIPOQ rs2241766 G>T, FTO rs9939609 A>T and ACE rs4340288 DIP variants among obese and non-obese Turkish Cypriot origin. Additionally, the correlation between these variants and biochemical and physical measurements were also evaluated to determine the possible biomarker for obesity in the population. Only FTO rs9939609 A>T polymorphism was associated with obesity and no association was observed with ADIPOQ rs2441666 G>T and ACE rs4340288 DIP. To conclude, FTO rs9939609 A allele found to have strong association with obesity in the population of Turkish Cypriots.
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Affiliation(s)
- Mahmut Cerkez Ergören
- Department of Medical Biology, Faculty of Medicine, Near East University, Nicosia, Cyprus; Research Center of Experimental Health Sciences (DESAM), Near East University, Nicosia, Cyprus.
| | - Gizem Söyler
- Department of Histology and Embryology, Faculty of Medicine, Near East University, Nicosia, Cyprus
| | - Hüseyin Sah
- Department of Histology and Embryology, Faculty of Veterinary Medicine, Near East University, Nicosia, Cyprus; Molecular Medicine Programs, Health Sciences Institute, Near East University, Nicosia, Cyprus
| | - Eda Becer
- Research Center of Experimental Health Sciences (DESAM), Near East University, Nicosia, Cyprus; Department of Biochemistry, Faculty of Pharmacy, Near East University, Nicosia, Cyprus
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Emerging Role of Adipocytokines in Type 2 Diabetes as Mediators of Insulin Resistance and Cardiovascular Disease. Can J Diabetes 2018; 42:446-456.e1. [PMID: 29229313 DOI: 10.1016/j.jcjd.2017.10.040] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 10/06/2017] [Accepted: 10/06/2017] [Indexed: 12/13/2022]
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Pal China S, Sanyal S, Chattopadhyay N. Adiponectin signaling and its role in bone metabolism. Cytokine 2018; 112:116-131. [PMID: 29937410 DOI: 10.1016/j.cyto.2018.06.012] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Revised: 06/06/2018] [Accepted: 06/09/2018] [Indexed: 12/14/2022]
Abstract
Adiponectin, the most prevalent adipo-cytokine in plasma plays critical metabolic and anti-inflammatory roles is fast emerging as an important molecular target for the treatment of metabolic disorders. Adiponectin action is critical in multiple organs including cardio-vascular system, muscle, liver, adipose tissue, brain and bone. Adiponectin signaling in bone has been a topic of active investigation lately. Human association studies and multiple mice models of gene deletion/modification failed to define a clear cause and effect of adiponectin signaling in bone. The most plausible reason could be the multimeric forms of adiponectin that display differential binding to receptors (adipoR1 and adipoR2) with cell-specific receptor variants in bone. Discovery of small molecule agonist of adipoR1 suggested a salutary role of this receptor in bone metabolism. The downstream signaling of adipoR1 in osteoblasts involves stimulation of oxidative phosphorylation leading to increased differentiation via the likely suppression of wnt inhibitor, sclerostin. On the other hand, the inflammation modulatory effect of adiponectin signaling suppresses the RANKL (receptor activator of nuclear factor κ-B ligand) - to - OPG (osteprotegerin) ratio in osteoblasts leading to the suppression of osteoclastogenic response. This review will discuss the adiponectin signaling and its role in skeletal homeostasis and critically assess whether adipoR1 could be a therapeutic target for the treatment of metabolic bone diseases.
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Affiliation(s)
- Shyamsundar Pal China
- Division of Endocrinology and CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226 031, India
| | - Sabyasachi Sanyal
- Division of Biochemistry, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226 031, India
| | - Naibedya Chattopadhyay
- Division of Endocrinology and CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226 031, India.
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20
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Adiponectin: A potential therapeutic target for metabolic syndrome. Cytokine Growth Factor Rev 2018; 39:151-158. [PMID: 29395659 DOI: 10.1016/j.cytogfr.2018.01.004] [Citation(s) in RCA: 124] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2018] [Accepted: 01/11/2018] [Indexed: 12/20/2022]
Abstract
Adiponectin is an important adipocytokine secreted chiefly by fat containing adipocytes, and plays a crucial role in glucose and lipid metabolism, inflammation and oxidative stress. Alterations in adiponectin levels have been shown to directly affect lipid and glucose metabolism that further increase the synthesis of lipids, free fatty acids and inflammatory cytokines. Changes in adiponectin levels also contribute to insulin resistance, obesity, cardiovascular diseases and type 2 diabetes. In the present review, we provide a comprehensive evaluation of the role of adiponectin and its molecular mechanisms in metabolic syndrome. Clinical improvement in adiponectin levels have been shown to positively modulate lipid and glucose metabolism, thus further substantiating its role in regulation of lipid and glucose metabolism. Currently adiponectin is being investigated as a potential therapeutic target for metabolic syndrome, although more research is required to understand the underlying mechanisms controlling adiponectin levels, including dietary and lifestyle interventions, that may target adiponectin as a therapeutic intervention in metabolic syndrome.
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21
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D'Incao RB, Tovo CV, Mattevi VS, Borges DO, Ulbrich JM, Coral GP, Ramos MJ, Meinhardt NG. Adipokine Levels Versus Hepatic Histopathology in Bariatric Surgery Patients. Obes Surg 2017; 27:2151-2158. [PMID: 28281237 DOI: 10.1007/s11695-017-2627-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Obesity is a worldwide prevalent disease and is an underlying factor of non-alcoholic fatty liver disease (NAFLD). It has been understood as a chronic inflammatory state, being associated with the production of adipokines. The aim of this study was to analyze the levels of adipokines in the serum, visceral, and subcutaneous fat and to compare them with hepatic histopathology in morbidly obese patients. METHODS This is a cross-sectional observational study, which analyzed the findings of liver biopsy in patients undergoing bariatric surgery and who had performed analysis of adipokines mRNA expression (adiponectin-ADIPOQ, leptin-LEP, and resistin-RETN) in subcutaneous and visceral adipose tissue and circulating adipokines in serum. Liver biopsies performed were evaluated according to Kleiner criteria. RESULTS The study analyzed 25 patients undergoing bariatric surgery. The sample was composed exclusively of women. There was a predominance of NAFLD, with 21 patients (84%) with intrahepatic fat accumulation. Twelve patients presented non-alcoholic steatohepatitis (NASH). Glycated hemoglobin levels (HbA1c) were elevated in NASH patients. ADIPOQ levels were directly correlated with high-density lipoprotein (HDL) cholesterol levels and inversely correlated with triglycerides and total cholesterol. LEP levels showed an inverse relationship with the degree of steatosis, and RETN levels showed an inverse relationship with fibrosis stages. CONCLUSION Serum LEP levels were reduced in the presence of increased levels of intrahepatic fat, and serum levels of RETN were diminished in the presence of NASH. HbA1c levels were higher in the presence of NASH, indirectly reflecting insulin resistance. Moreover, ADIPOQ levels were related to blood lipid profile.
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Affiliation(s)
- Rafael Bergesch D'Incao
- Medicine at Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua São Manoel, 95 / 403; Bairro Rio Branco, Porto Alegre, CEP 90620-110, Brazil.
| | - Cristiane Valle Tovo
- Department and at Post Graduation Program, Hepatology at UFCSPA, Porto Alegre, Brazil
| | - Vanessa Suñé Mattevi
- Department and at Post Graduation Programs, Biosciences, Pathology and Health Sciences at UFCSPA, Porto Alegre, Brazil
| | | | - Jane Maria Ulbrich
- Department of Pathology from Hospital Nossa Senhora da Conceição (HNSC), Porto Alegre, Brazil
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JafariNasabian P, Inglis JE, Reilly W, Kelly OJ, Ilich JZ. Aging human body: changes in bone, muscle and body fat with consequent changes in nutrient intake. J Endocrinol 2017; 234:R37-R51. [PMID: 28442508 DOI: 10.1530/joe-16-0603] [Citation(s) in RCA: 181] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 04/25/2017] [Indexed: 12/14/2022]
Abstract
Aging affects almost all physiological processes, but changes in body composition and body phenotype are most observable. In this review, we focus on these changes, including loss of bone and muscle and increase in body fat or redistribution of the latter, possibly leading to osteosarcopenic obesity syndrome. We also address low-grade chronic inflammation, prevalent in aging adults and a cause of many disorders including those associated with body composition. Changes in dietary intake and nutritional requirements of older individuals, that all may lead to some disturbances on tissue and organ levels, are discussed as well. Finally, we discuss the hormonal changes in the aging body, considering each of the tissues, bone, muscle and fat as separate endocrine organs, but yet in the continuous interface and communication with each other. Although there are still many unanswered questions in this field, this review will enable the readers to better understand the aging human body and measures needing to be implemented toward reducing impaired health and disability in older individuals.
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Affiliation(s)
- Pegah JafariNasabian
- Department of NutritionFood and Exercise Sciences, Florida State University, Tallahassee, Florida, USA
| | - Julia E Inglis
- Department of NutritionFood and Exercise Sciences, Florida State University, Tallahassee, Florida, USA
| | - Wendimere Reilly
- Department of NutritionFood and Exercise Sciences, Florida State University, Tallahassee, Florida, USA
| | | | - Jasminka Z Ilich
- Department of NutritionFood and Exercise Sciences, Florida State University, Tallahassee, Florida, USA
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23
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Hossain MM, Murali MR, Kamarul T. Genetically modified mesenchymal stem/stromal cells transfected with adiponectin gene can stably secrete adiponectin. Life Sci 2017; 182:50-56. [PMID: 28606849 DOI: 10.1016/j.lfs.2017.06.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 06/05/2017] [Accepted: 06/09/2017] [Indexed: 12/13/2022]
Abstract
AIMS Mesenchymal stem/stromal cells (MSCs) hold promises for the treatment of diverse diseases and regeneration of injured tissues. Genetic modification of MSCs through gene delivery might enhance their therapeutic potential. Adiponectin has been appeared as a potential biomarker for predicting various diseases. Plasma adiponectin levels are negatively correlated with various metabolic and vascular diseases and supplementation of exogenous adiponectin ameliorates the diseases. This study aims to develop adiponectin secreting genetically modified MSCs (GM-MSCs) as a potent strategic tool to complement endogenous adiponectin for the treatment of adiponectin deficiency diseases. MAIN METHODS Human bone marrow derived MSCs were isolated, expanded in vitro and transfected with adiponectin gene containing plasmid vector. Total RNA was extracted and cDNA was prepared by reverse transcription polymerase chain reaction (RT-PCR). The expression of adiponectin gene and protein in GM-MSCs was analyzed by PCR and Western blotting respectively. The secretion of adiponectin protein from GM-MSCs was analyzed by enzyme-linked immunosorbent assay. KEY FINDINGS The expression of adiponectin gene and plasmid DNA was detected in GM-MSCs but not in control group of MSCs. Adiponectin gene expression was detected in GM-MSCs at 2, 7, 14, 21 and 28days after transfection. Western blotting analysis revealed the expression of adiponectin protein only in GM-MSCs. The GM-MSCs stably secreted adiponectin protein into culture media at least for 4weeks. SIGNIFICANCE GM-MSCs express and secret adiponectin protein. Therefore, these adiponectin secreting GM-MSCs could be instrumental for the supplementation of adiponectin in the treatment of adiponectin deficiency related diseases.
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Affiliation(s)
- Md Murad Hossain
- Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
| | - Malliga Raman Murali
- Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Tunku Kamarul
- Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; Director, University Malay Medical Center, 50603 Kuala Lumpur, Malaysia.
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Bossolasco P, Cancello R, Doretti A, Morelli C, Silani V, Cova L. Adiponectin levels in the serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients: possible influence on neuroinflammation? J Neuroinflammation 2017; 14:85. [PMID: 28427413 PMCID: PMC5397697 DOI: 10.1186/s12974-017-0861-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 04/05/2017] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Adiponectin (APN) is a key player in energy homeostasis strictly associated with cerebrovascular and neurodegenerative diseases. Since APN also belongs to anti-inflammatory-acting adipokines and may influence both neuroinflammation and neurodegenerative processes, we decided to study the APN levels in amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. METHODS We assessed APN levels by ELISA immunoassay in both the serum and cerebrospinal fluid of a cohort of familial and sporadic ALS patients, characterized by normal body mass index and absence of dysautonomic symptoms. The screening of serum APN levels was also performed in patients affected by other neurological disorders, including fronto-temporal dementia (FTD) patients. Means were compared using the non-parametric Wilcoxon test, and Pearson's or Spearman's rho was used to assess correlations between variables. RESULTS In the whole ALS group, serum APN levels were not different when compared to the age- and sex-matched control group (CTR), but a gender-specific analysis enlightened a significant opposite APN trend between ALS males, characterized by lower values (ALS 9.8 ± 5.2 vs. CTR 15 ± 9.7 μg/ml), and ALS females, showing higher amounts (ALS 26.5 ± 11.6 vs. CTR 14.6 ± 5.2 μg/ml). This sex-linked difference was significantly enhanced in familial ALS cases (p ≤ 0.01). The APN levels in ALS cerebrospinal fluids were unrelated to serum values and not linked to sex and/or familiarity of the disease. Finally, the screening of serum APN levels in patients affected by other neurological disorders revealed the highest serum values in FTD patients. CONCLUSIONS Opposite serum APN levels are gender-related in ALS and altered in several neurological disorders, with the highest values in FTD, which shares with ALS several overlapping and neuropathological features. Further investigations are needed to clarify the possible involvement of APN in neuroinflammation and neurodegeneration. Possible involvement of APN in neuroinflammatory neurodegenerative diseases.
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Affiliation(s)
- Patrizia Bossolasco
- Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, piazzale Brescia 20, 20149, Milan, Italy
| | - Raffaella Cancello
- Diabetes Research Laboratory, IRCCS, Istituto Auxologico Italiano, via Ariosto 13, 20145, Milan, Italy
| | - Alberto Doretti
- Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, piazzale Brescia 20, 20149, Milan, Italy
| | - Claudia Morelli
- Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, piazzale Brescia 20, 20149, Milan, Italy
| | - Vincenzo Silani
- Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, piazzale Brescia 20, 20149, Milan, Italy.,"Dino Ferrari" Centre, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, via Sforza 35, 20122, Milan, Italy
| | - Lidia Cova
- Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, piazzale Brescia 20, 20149, Milan, Italy. .,Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, via Zucchi 18, 20095, Cusano Milanino, Milan, Italy.
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25
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Costamagna D, Mommaerts H, Sampaolesi M, Tylzanowski P. Noggin inactivation affects the number and differentiation potential of muscle progenitor cells in vivo. Sci Rep 2016; 6:31949. [PMID: 27573479 PMCID: PMC5004166 DOI: 10.1038/srep31949] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Accepted: 07/28/2016] [Indexed: 10/25/2022] Open
Abstract
Inactivation of Noggin, a secreted antagonist of Bone Morphogenetic Proteins (BMPs), in mice leads, among others, to severe malformations of the appendicular skeleton and defective skeletal muscle fibers. To determine the molecular basis of the phenotype, we carried out a histomorphological and molecular analysis of developing muscles Noggin(-/-) mice. We show that in 18.5 dpc embryos there is a marked reduction in muscle fiber size and a failure of nuclei migration towards the cell membrane. Molecularly, the absence of Noggin results in an increased BMP signaling in muscle tissue as shown by the increase in SMAD1/5/8 phosphorylation, concomitant with the induction of BMP target genes such as Id1, 2, 3 as well as Msx1. Finally, upon removal of Noggin, the number of mesenchymal Pax7(+) muscle precursor cells is reduced and they are more prone to differentiate into adipocytes in vitro. Thus, our results highlight the importance of Noggin/BMP balance for myogenic commitment of early fetal progenitor cells.
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Affiliation(s)
- Domiziana Costamagna
- Translational Cardiomyology Lab, Stem Cell Biology and Embryology, Dept. Development and Regeneration, KU Leuven, Belgium.,Laboratory of Experimental Medicine and Clinical Pathology, Dept. Clinical and Biological Sciences, University of Turin, Italy
| | - Hendrik Mommaerts
- Department of Development and Regeneration, Laboratory for Developmental and Stem Cell Biology, Skeletal Biology and Engineering Research Centre, KU Leuven, Belgium
| | - Maurilio Sampaolesi
- Translational Cardiomyology Lab, Stem Cell Biology and Embryology, Dept. Development and Regeneration, KU Leuven, Belgium.,Division of Human Anatomy, Dept. of Public Health, Experimental and Forensic Medicine, University of Pavia, Italy
| | - Przemko Tylzanowski
- Department of Development and Regeneration, Laboratory for Developmental and Stem Cell Biology, Skeletal Biology and Engineering Research Centre, KU Leuven, Belgium.,Department of Biochemistry and Molecular Biology, Medical University, Lublin, Poland
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26
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Ahmad S, Shah M, Ahmed J, Khan A, Hussain H, McVey M, Ali A. Association of hypoadiponectemia with smokeless/dipping tobacco use in young men. BMC Public Health 2015; 15:1072. [PMID: 26482904 PMCID: PMC4615338 DOI: 10.1186/s12889-015-2409-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 10/12/2015] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Low levels of adiponectin, an adipocytokine with anti-diabetic, antiatherogenic and cardioprotective properties, is associated with increased risk of coronary disease in young men. Previous studies have demonstrated that smokeless tobacco is linked with a reduction of plasma adiponectin levels. However, the influence of smokeless tobacco (dipping tobacco) on plasma adiponectin levels still remains unknown. This study was conducted to assess the plasma adiponectin levels in young men who were using dipping tobacco. METHODS This was a community based study, which consisted of 186 young lean healthy males aged 20 to 35 years. Among these, 96 men were dipping tobacco users (BMI = 23.07 ± 2.68) and 90 were non-dipping tobacco users (BMI = 23.67 ± 1.46). Serum adiponectin levels were assessed by Enzyme Linked ImmunoSorbent Assay (ELISA). RESULTS A statistically significant difference in the mean adiponectin level between tobacco dipper and non-dipper groups was observed (p = 0.0001). A significant difference between the two groups was also observed in baseline parameters including triglyceride and random blood sugar levels (p < 0.05). However, no significant difference was observed between the two groups in other clinical parameters. CONCLUSIONS Findings of this study suggest that dipping tobacco use was significantly associated with low level of adiponetin in community dwelling young males. This emphasizes the importance of developing community intervention to reduce the use of dipping tobacco, which will reduce the tobacco associated disease burden in the community and will improve public health.
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Affiliation(s)
- Sardar Ahmad
- Department of Physiology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
| | - Mohsin Shah
- Department of Physiology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
- Institute of Basic Medical Sciences, Khyber Medical University, Adjacent PDA building, Phase 5, Hayat Abad, Peshawar, Pakistan.
| | - Jawad Ahmed
- Department of Physiology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
| | - Aslam Khan
- Department of Pharmacology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
| | - Hamid Hussain
- Institute of Public Health and Social Sciences, Khyber Medical University, Peshawar, Pakistan.
| | - Mary McVey
- School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, UK.
| | - Asif Ali
- Department of Pathology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
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27
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Gnanou JV, Caszo BA, Khalil KM, Abdullah SL, Knight VF, Bidin MZ. Effects of Ramadan fasting on glucose homeostasis and adiponectin levels in healthy adult males. J Diabetes Metab Disord 2015; 14:55. [PMID: 26155596 PMCID: PMC4494190 DOI: 10.1186/s40200-015-0183-9] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Accepted: 06/20/2015] [Indexed: 01/08/2023]
Abstract
BACKGROUND Adiponectin is a hormone secreted by adipocytes during the fasting phase of the fast-fed cycle. Ramadan fasting involves prolonged fasting for up to twelve hours and thus could lead to increased secretion of adiponectin by adipocytes. However, studies on the role of adiponectin on glucose and body weight homeostasis during Ramadan fasting is still a matter of controversy. Thus the specific aim of this study was to assess the effect of fasting during Ramadan on the adiponectin levels, body weight and glucose homeostasis in healthy male Malaysian subjects. METHODS Twenty healthy male (19-23 years) Muslim subjects were followed up during the fasting month of Ramadan. Anthropometry and blood samples were taken one week before and during the fourth week of fasting. Plasma glucose, insulin and adiponectin were estimated and insulin sensitivity indices were estimated using the Homeostasis Model Assessment. RESULTS Subjects experienced a significant decrease in body weight (2.4 %, p < 0.001) and body mass index (5.5 %, p < 0.01). There was also a significant decrease of 12.3 %, 52.8 % and 45.6 % of plasma glucose, insulin and adiponectin respectively (p < 0.01). The drop in adiponectin was positively correlated with the decrease in body weight (r = 0.45, p < 0.05). There was also a significant increase in insulin sensitivity and a decrease in insulin resistance (p < 0.01). CONCLUSIONS These results indicate that Ramadan fasting in young healthy individuals has a positive impact on the maintenance of glucose homeostasis. It also shows that adiponectin levels dropped along with significant loss in weight. We feel caloric restriction during the Ramadan fasting is in itself sufficient to improve insulin sensitivity in healthy individuals.
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Affiliation(s)
- Justin V Gnanou
- Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kem Sungai Besi, Kuala Lumpur, 57000 Malaysia
| | - Brinnell A Caszo
- Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kem Sungai Besi, Kuala Lumpur, 57000 Malaysia
| | - Khalifah M Khalil
- Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kem Sungai Besi, Kuala Lumpur, 57000 Malaysia
| | - Shahidah L Abdullah
- Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kem Sungai Besi, Kuala Lumpur, 57000 Malaysia
| | - Victor F Knight
- Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kem Sungai Besi, Kuala Lumpur, 57000 Malaysia
| | - Mohd Z Bidin
- Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kem Sungai Besi, Kuala Lumpur, 57000 Malaysia
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Bou M, Todorčević M, Rodríguez J, Capilla E, Gutiérrez J, Navarro I. Interplay of adiponectin, TNFα and insulin on gene expression, glucose uptake and PPARγ, AKT and TOR pathways in rainbow trout cultured adipocytes. Gen Comp Endocrinol 2014; 205:218-25. [PMID: 24846393 DOI: 10.1016/j.ygcen.2014.05.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Revised: 04/30/2014] [Accepted: 05/04/2014] [Indexed: 12/15/2022]
Abstract
Adipose tissue is being increasingly recognized as an important endocrine organ that produces and releases a variety of factors. In the present study we have evaluated in primary cultures of rainbow trout adipocytes, obtained from visceral adipose tissue, the interplay of the adiponectin system, TNFα and insulin at a transcriptional level and, their effects on the adipogenic transcription factor PPARγ, as well as on the activation of main insulin signaling pathways. Likewise, the implication of these adipokines in the regulation of glucose uptake in the adipocyte and their interactions with insulin or IGF-I were also evaluated. Similarly to the mammalian model, insulin enhanced adiponectin gene expression, while it exerted a negative modulation on adiponectin receptors. TNFα increased the mRNA levels of adiponectin receptor 1, but neither adiponectin nor TNFα modulated each other expression. Therefore, the reciprocal suppressive effect of both adipokines previously reported in mammals was not present in this model. Furthermore, the anti-adipogenic effect of TNFα was revealed by the down-regulation of PPARγ at a protein level, meanwhile adiponectin increased PPARγ expression in insulin-stimulated adipocytes, supporting its insulin-sensitizing role. Both adipokines stimulated glucose uptake without modifying AKT or TOR phosphorylation; however, glucose uptake in insulin-treated adipocytes was enhanced by TNFα but not by adiponectin. All in all, these results contribute to gain knowledge on the role of adipokines in rainbow trout adipose tissue and, to better understand the mechanisms that regulate glucose metabolism in this species.
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Affiliation(s)
- Marta Bou
- Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain
| | | | - Júlia Rodríguez
- Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain
| | - Encarnación Capilla
- Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain
| | - Joaquim Gutiérrez
- Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain
| | - Isabel Navarro
- Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain.
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Ilich JZ, Kelly OJ, Inglis JE, Panton LB, Duque G, Ormsbee MJ. Interrelationship among muscle, fat, and bone: connecting the dots on cellular, hormonal, and whole body levels. Ageing Res Rev 2014; 15:51-60. [PMID: 24632496 DOI: 10.1016/j.arr.2014.02.007] [Citation(s) in RCA: 193] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 01/25/2014] [Accepted: 02/28/2014] [Indexed: 12/24/2022]
Abstract
While sarcopenia and sarcopenic obesity have been recognized in the last decade, a combined concept to include decreased muscle mass and strength, as well as decreased bone mass with coexistence of adiposity is discussed here. We introduce a new term, osteopenic obesity, and operationalize its meaning within the context of osteopenia and obesity. Next, we consolidate osteopenic obesity with the already existing and more familiar term, sarcopenic obesity, and delineate the resulting combined condition assigning it the term osteosarcopenic obesity. Identification and possible diagnosis of each condition are discussed, as well as the interactions of muscle, fat and bone tissues on cellular level, considering their endocrine features. Special emphasis is placed on the mesenchymal stem cell commitment into osteoblastogenic, adipogenic and myogenic lineages and causes of its deregulation. Based on the presented evidence and as expounded within the text, it is reasonable to say that under certain conditions, osteoporosis and sarcopenia could be the obesity of bone and muscle, respectively, with the term osteosarcopenic obesity as an encompassment for all.
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