|
1
|
Wen RM, Wang HX. Effect of adipokines on bone marrow mesenchymal stem cell function. World J Stem Cells 2025; 17:106150. [DOI: 10.4252/wjsc.v17.i5.106150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 03/23/2025] [Accepted: 04/09/2025] [Indexed: 05/26/2025] Open
Abstract
During excessive adipose tissue accumulation, various adipokines such as visfatin, chemerin, vaspin, and adiponectin are released into systemic circulation, thereby influencing metabolic tissue function throughout the body. As multifunctional signaling molecules secreted by adipose tissue, adipokines play a pivotal role in metabolic regulation, inflammatory response, and tissue homeostasis. Recent studies have demonstrated that adipokines can influence skeletal system repair and regeneration by modulating bone marrow-derived mesenchymal stem cell (BMSC) proliferation, differentiation, migration, and immunomodulatory functions. However, different adipokines have distinct roles in regulating BMSC function, but their underlying molecular mechanisms are not fully understood. In this review, we systematically summarize the specific mechanisms of action and potential clinical applications of visfatin, chemerin, vaspin, and adiponectin on BMSC function in order to reveal new mechanisms of interaction between adipokines and BMSCs. The aim is to provide a theoretical basis for targeted treatment strategies for bone diseases targeting adipokines.
Collapse
Affiliation(s)
- Rui-Ming Wen
- School of Sports Health, Shenyang Sport University, Shenyang 110102, Liaoning Province, China
| | - Hai-Xia Wang
- College of Exercise and Health, Shenyang Sport University, Shenyang 110102, Liaoning Province, China
| |
Collapse
|
|
2
|
Wargent ET, Kępczyńska MA, Kaspersen MH, Ulven ER, Arch JRS, Ulven T, Stocker CJ. Chronic administration of hydrolysed pine nut oil to mice improves insulin sensitivity and glucose tolerance and increases energy expenditure via a free fatty acid receptor 4-dependent mechanism. Br J Nutr 2024; 132:13-20. [PMID: 38751244 DOI: 10.1017/s0007114524000965] [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] [Indexed: 05/28/2024]
Abstract
A healthy diet is at the forefront of measures to prevent type 2 diabetes. Certain vegetable and fish oils, such as pine nut oil (PNO), have been demonstrated to ameliorate the adverse metabolic effects of a high-fat diet. The present study investigates the involvement of the free fatty acid receptors 1 (FFAR1) and 4 (FFAR4) in the chronic activity of hydrolysed PNO (hPNO) on high-fat diet-induced obesity and insulin resistance. Male C57BL/6J wild-type, FFAR1 knockout (-/-) and FFAR4-/- mice were placed on 60 % high-fat diet for 3 months. Mice were then dosed hPNO for 24 d, during which time body composition, energy intake and expenditure, glucose tolerance and fasting plasma insulin, leptin and adiponectin were measured. hPNO improved glucose tolerance and decreased plasma insulin in the wild-type and FFAR1-/- mice, but not the FFAR4-/- mice. hPNO also decreased high-fat diet-induced body weight gain and fat mass, whilst increasing energy expenditure and plasma adiponectin. None of these effects on energy balance were statistically significant in FFAR4-/- mice, but it was not shown that they were significantly less than in wild-type mice. In conclusion, chronic hPNO supplementation reduces the metabolically detrimental effects of high-fat diet on obesity and insulin resistance in a manner that is dependent on the presence of FFAR4.
Collapse
Affiliation(s)
- Edward Taynton Wargent
- Institute of Translational Medicine, Clore Laboratory, University of Buckingham, Buckingham, MK18 1EG, UK
| | - Małgorzata A Kępczyńska
- Institute of Translational Medicine, Clore Laboratory, University of Buckingham, Buckingham, MK18 1EG, UK
| | - Mads H Kaspersen
- Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230 Odense, Denmark
| | - Elisabeth Rexen Ulven
- Department of Drug Design and Pharmacology, University of Copenhagen, 2100Copenhagen, Denmark
| | - Jonathan R S Arch
- Institute of Translational Medicine, Clore Laboratory, University of Buckingham, Buckingham, MK18 1EG, UK
| | - Trond Ulven
- Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230 Odense, Denmark
- Department of Drug Design and Pharmacology, University of Copenhagen, 2100Copenhagen, Denmark
| | | |
Collapse
|
|
3
|
Deng H, Ai M, Cao Y, Cai L, Guo X, Yang X, Yi G, Fu M. Potential Protective Function of Adiponectin in Diabetic Retinopathy. Ophthalmol Ther 2023; 12:1519-1534. [PMID: 37000404 PMCID: PMC10164206 DOI: 10.1007/s40123-023-00702-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 03/06/2023] [Indexed: 04/01/2023] Open
Abstract
Adiponectin, one of the most ubiquitous adipokines found in the blood, plays a major role in glucolipid metabolism and energy metabolism and regulation. In recent years, a growing body of research indicates that adiponectin also plays a significant role in diabetic retinopathy. In the present review, we specifically address the protective effects of adiponectin on the development and progression of diabetic retinopathy through improvement in insulin resistance, alleviation of oxidative stress, limiting of inflammation, and prevention of vascular remodeling, with the aim to explore new potential approaches and targets for the prevention and treatment of diabetic retinopathy.
Collapse
Affiliation(s)
- Hui Deng
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue Middle, Haizhu, Guangzhou, 510280, Guangdong, China
- The Second Clinical School of Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Meichen Ai
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue Middle, Haizhu, Guangzhou, 510280, Guangdong, China
- The Second Clinical School of Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Yuchen Cao
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue Middle, Haizhu, Guangzhou, 510280, Guangdong, China
- The Second Clinical School of Southern Medical University, Guangzhou, 510280, Guangdong, China
- Plastic Surgery Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100144, China
| | - Liyang Cai
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue Middle, Haizhu, Guangzhou, 510280, Guangdong, China
- The Second Clinical School of Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Xi Guo
- School of Rehabilitation Sciences, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Xiongyi Yang
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue Middle, Haizhu, Guangzhou, 510280, Guangdong, China
- The Second Clinical School of Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Guoguo Yi
- Department of Ophthalmology, The Sixth Affiliated Hospital of Sun Yat-Sen University, No. 26, Erheng Road, Yuancun, Tianhe, Guangzhou, 510230, Guangdong, China.
| | - Min Fu
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue Middle, Haizhu, Guangzhou, 510280, Guangdong, China.
- The Second Clinical School of Southern Medical University, Guangzhou, 510280, Guangdong, China.
| |
Collapse
|
|
4
|
Shklyaev SS, Melnichenko GA, Volevodz NN, Falaleeva NA, Ivanov SA, Kaprin AD, Mokrysheva NG. Adiponectin: a pleiotropic hormone with multifaceted roles. PROBLEMY ENDOKRINOLOGII 2021; 67:98-112. [PMID: 35018766 PMCID: PMC9753852 DOI: 10.14341/probl12827] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 10/22/2021] [Indexed: 05/28/2023]
Abstract
Adipose tissue mostly composed of different types of fat is one of the largest endocrine organs in the body playing multiple intricate roles including but not limited to energy storage, metabolic homeostasis, generation of heat, participation in immune functions and secretion of a number of biologically active factors known as adipokines. The most abundant of them is adiponectin. This adipocite-derived hormone exerts pleiotropic actions and exhibits insulin-sensitizing, antidiabetic, anti-obesogenic, anti-inflammatory, antiatherogenic, cardio- and neuroprotective properties. Contrariwise to its protective effects against various pathological events in different cell types, adiponectin may have links to several systemic diseases and malignances. Reduction in adiponectin levels has an implication in COVID-19-associated respiratory failure, which is attributed mainly to a phenomenon called 'adiponectin paradox'. Ample evidence about multiple functions of adiponectin in the body was obtained from animal, mostly rodent studies. Our succinct review is entirely about multifaceted roles of adiponectin and mechanisms of its action in different physiological and pathological states.
Collapse
Affiliation(s)
- S. S. Shklyaev
- National Research Center for Endocrinology of the Ministry of Health of the Russian Federation;
A. Tsyb Medical Radiological Research Center — Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
| | - G. A. Melnichenko
- National Research Center for Endocrinology of the Ministry of Health of the Russian Federatio
| | - N. N. Volevodz
- National Research Center for Endocrinology of the Ministry of Health of the Russian Federatio
| | - N. A. Falaleeva
- A. Tsyb Medical Radiological Research Center — Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
| | - S. A. Ivanov
- A. Tsyb Medical Radiological Research Center — Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
| | - A. D. Kaprin
- A. Tsyb Medical Radiological Research Center — Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
| | - N. G. Mokrysheva
- National Research Center for Endocrinology of the Ministry of Health of the Russian Federation
| |
Collapse
|
|
5
|
Mahmoud AA, Moghazy HM, Yousef LM, Mohammad AN. Adiponectin rs2241766 and rs266729 gene polymorphisms in non-alcoholic fatty liver disease. GENE REPORTS 2019. [DOI: 10.1016/j.genrep.2019.100381] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
6
|
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.
Collapse
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
| |
Collapse
|
|
7
|
Liu Z, Liang S, Que S, Zhou L, Zheng S, Mardinoglu A. Meta-Analysis of Adiponectin as a Biomarker for the Detection of Metabolic Syndrome. Front Physiol 2018; 9:1238. [PMID: 30333754 PMCID: PMC6176651 DOI: 10.3389/fphys.2018.01238] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 08/15/2018] [Indexed: 12/15/2022] Open
Abstract
Previous studies revealed the potential significance of circulating adiponectin levels with respect to the diagnosis and prediction of metabolic syndrome, but uncertainty has been noted across different cohorts. Systematic evaluation was performed for diagnostic accuracy and predictivity of adiponectin variation for metabolic syndrome in enrolled studies including 1,248 and 6,020 subjects, respectively. Adiponectin can identify metabolic syndrome with moderate accuracy (area under the curve = 0.81, 95% CI: 0.77–0.84). Heterogeneity analysis revealed that an increasing index of insulin resistance was independently associated with improving the performance of adiponectin upon metabolic syndrome diagnosis (ratio of diagnostic odds ratio = 3.89, 95% CI: 1.13–13.9). In addition, reductions in adiponectin were associated with increasing metabolic syndrome incidence in a linear dose-response manner. The risk of hypoadiponectinemia with metabolic syndrome was especially increased in men (P < 0.05). Further Mendelian randomization analysis identified that the amplified risk could be attributed to increased susceptibility (up to 7%) to insulin resistance compared with women. In conclusion, adiponectin measurement might have potential benefits in the detection of metabolic syndrome. Factors that affect insulin resistance should be considered for adjustment in future assessments.
Collapse
Affiliation(s)
- Zhengtao Liu
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Hangzhou, China.,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shuheng Liang
- Department of Pediatrics, Women and Children's Hospital of Guangxi, Nanning, China
| | - Shuping Que
- Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden
| | - Lin Zhou
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Hangzhou, China.,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shusen Zheng
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Hangzhou, China.,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Adil Mardinoglu
- Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.,Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.,Centre for Host-Microbiome Interactions, Dental Institute, King's College London, London, United Kingdom
| |
Collapse
|
|
8
|
Sarmento-Cabral A, L-López F, Luque RM. Adipokines and Their Receptors Are Widely Expressed and Distinctly Regulated by the Metabolic Environment in the Prostate of Male Mice: Direct Role Under Normal and Tumoral Conditions. Endocrinology 2017; 158:3540-3552. [PMID: 28938461 DOI: 10.1210/en.2017-00370] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 08/03/2017] [Indexed: 12/15/2022]
Abstract
Adipose tissue-derived adipokines (i.e., leptin/adiponectin/resistin) play important roles in the regulation of several pathophysiologic processes through the activation of specific receptors. However, although adipokines and their receptors are widely distributed in many tissues and exhibit a clear modulation according to particular metabolic conditions (e.g., obesity and/or fasting), their expression, regulation, and putative action on normal prostate glands (PGs; a hormone-dependent organ tightly regulated by the endocrine-metabolic milieu) are still to be defined. Different in vivo/in vitro models were used to comprehensively characterize the expression pattern and actions of different adipokine systems (i.e., leptin/adiponectin/resistin/receptors) in mouse PGs. Adiponectin, resistin, and adiponectin receptors (1 and 2) and leptin receptor are coexpressed at different levels in PG cells, wherein they are finely regulated under fasting and/or obesity conditions. Furthermore, treatment with different adipokines exerted both homologous and heterologous regulation of specific adipokines/receptor-synthesis and altered the expression of key proliferation and oncogenesis markers (i.e., Ki67/c-Myc/p53) in mouse PG cell cultures, wherein some of these actions might be elicited through extracellular signal-regulated kinase (ERK) activation. Moreover, treatment with leptin, adiponectin, and resistin differentially regulated key functional parameters [i.e., proliferation and migration capacity and/or prostate-specific antigen (PSA) secretion] in human normal and/or tumoral prostate cell lines. Altogether, our data show that various adipokine and receptor systems are differentially expressed in normal PG cells; that their expression is under a complex ligand- and receptor-selective regulation under extreme metabolic conditions; and that they mediate distinctive and common direct actions in normal and tumoral PG cells (i.e., homologous and heterologous regulation of ligand and receptor synthesis, ERK signaling activation, modulation of proliferation markers, proliferation and migration capacity, and PSA secretion), suggesting a relevant role of these systems in the regulation of PG pathophysiology.
Collapse
Affiliation(s)
- André Sarmento-Cabral
- Maimonides Institute of Biomedical Research of Cordoba, 14004 Cordoba, Spain
- Reina Sofía University Hospital, 14004 Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition, 14004 Cordoba, Spain
- Internacional Campus of Excellence on Agrifood, 14004 Cordoba, Spain
| | - Fernando L-López
- Maimonides Institute of Biomedical Research of Cordoba, 14004 Cordoba, Spain
- Reina Sofía University Hospital, 14004 Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition, 14004 Cordoba, Spain
- Internacional Campus of Excellence on Agrifood, 14004 Cordoba, Spain
| | - Raúl M Luque
- Maimonides Institute of Biomedical Research of Cordoba, 14004 Cordoba, Spain
- Reina Sofía University Hospital, 14004 Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition, 14004 Cordoba, Spain
- Internacional Campus of Excellence on Agrifood, 14004 Cordoba, Spain
| |
Collapse
|
|
9
|
Delitala AP, Capobianco G, Delitala G, Cherchi PL, Dessole S. Polycystic ovary syndrome, adipose tissue and metabolic syndrome. Arch Gynecol Obstet 2017. [DOI: 10.1007/s00404-017-4429-2] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
|
|
10
|
Derosa G, Maffioli P, Sahebkar A. Improvement of plasma adiponectin, leptin and C-reactive protein concentrations by orlistat: a systematic review and meta-analysis. Br J Clin Pharmacol 2016; 81:819-834. [PMID: 26717446 PMCID: PMC4834599 DOI: 10.1111/bcp.12874] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2015] [Revised: 12/07/2015] [Accepted: 12/14/2015] [Indexed: 12/27/2022] Open
Abstract
AIMS To conduct a systematic review and meta-analysis of relevant randomized clinical trials (RCTs) to ascertain the effect size of orlistat in modulating plasma levels of adipokines, ghrelin and C-reactive protein (CRP). METHODS Medline, SCOPUS, Web of Science and Google Scholar databases were searched. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was quantitatively assessed using I(2) index. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of duration of treatment, percentage change in body mass index (BMI) and baseline BMI values as potential confounders of the estimated effect size. RESULTS Meta-analysis suggested a significant increase in plasma levels of adiponectin [weighted mean difference (WMD): 19.18%, 95% confidence interval (CI): 5.80, 32.57, p = 0.005] and significant reductions in plasma levels of leptin (WMD: -13.24%, 95% CI: -20.69, -5.78, p = 0.001) and CRP (WMD: -11.52%, 95% CI: -16.55, -6.49, p < 0.001) following treatment with orlistat. In meta-regression, changes in plasma concentrations of adiponectin, leptin and CRP were associated with duration of treatment, but not with either change in BMI or baseline BMI values. CONCLUSION Orlistat is effective in increasing plasma concentrations of adiponectin and decreasing those of leptin and CRP.
Collapse
Affiliation(s)
- Giuseppe Derosa
- Department of Internal Medicine and TherapeuticsUniversity of Pavia and Fondazione IRCCS Policlinico S. MatteoPaviaItaly
- Center for the Study of Endocrine‐Metabolic Pathophysiology and Clinical ResearchUniversity of PaviaPaviaItaly
- Molecular Medicine LaboratoryUniversity of PaviaPaviaItaly
| | - Pamela Maffioli
- Department of Internal Medicine and TherapeuticsUniversity of Pavia and Fondazione IRCCS Policlinico S. MatteoPaviaItaly
- PhD School in Experimental MedicineUniversity of PaviaPaviaItaly
| | - Amirhossein Sahebkar
- Biotechnology Research CenterMashhad University of Medical SciencesMashhadIran
- Metabolic Research Centre, Royal Perth HospitalSchool of Medicine and Pharmacology, University of Western AustraliaPerthAustralia
| |
Collapse
|
|
11
|
Raj R, Bhatti JS, Badada SK, Ramteke PW. Genetic basis of dyslipidemia in disease precipitation of coronary artery disease (CAD) associated type 2 diabetes mellitus (T2DM). Diabetes Metab Res Rev 2015; 31:663-671. [PMID: 25470794 DOI: 10.1002/dmrr.2630] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Accepted: 11/18/2014] [Indexed: 01/09/2023]
Abstract
Type 2 diabetes mellitus (T2DM) and its complications are linked to environmental, clinical, and genetic factors. This review analyses the disorders of lipids and their genetics with respect to coronary artery disease (CAD) associated with T2DM. Cell organelles, hepatitis C-virus infection, reactive oxygen species produced in mitochondria, and defective insulin signaling due to the arrest of G1 phase to S phase transition of β-cells have significant roles in the precipitation of the diseases. Adiponectin is anti-inflammatory and anti-atherosclerotic and improves insulin resistance. Low-density lipoprotein (LDL) is atherosclerotic, and LDL-cholesterol in T2DM is associated with high-cardiovascular risk. Further, LDL cholesterol reduction significantly reduces cardiovascular morbidity and mortality. High-density lipoprotein (HDL) is also anti-atherosclerotic due to HDL associated paraoxonase-1 serum enzyme, which prevents LDL oxidative modifications and the development of CAD. Moreover, elevated apolipoprotein B and apolipoprotein A-I (ApoB/ApoA-I) ratio in plasma is also a risk factor for CAD. LDL receptor, adiponectin, and endocannabinoid receptor-1 genes are independently associated with CAD and T2DM. Polymorphism of Apo E2 (epsilon2) is a positive factor to increase the T2DM risk and Apo E4 (epsilon4) is a negative factor to reduce the disease risk. Taq 1B polymorphism of cholesterol ester transfer protein (CETP) gene contributes to the development of atherosclerosis, whereas haplotypes of APOA5, APOC3, APOC4, and APOC5 genes are in the same cluster and are independently associated with high plasma triglyceride level, CAD and T2DM. In conclusion, because various genes, LDLR, CETP, APOA5, Apo E, Apo B, and Apo A-I, are associated with the precipitation of CAD associated with T2DM, a personalized diet-gene intervention therapy may be advocated to reduce the disease precipitation.
Collapse
Affiliation(s)
- Resal Raj
- Department of Computational Biology and Bioinformatics, Sam Higginbottom Institute of Agriculture, Technology and Sciences, Deemed to be University, Allahabad, India
| | - Jasvinder Singh Bhatti
- Department of Biotechnology & Bioinformatics, SGGS College, Sector 26, Chandigarh, India
| | | | - Pramod W Ramteke
- Department of Biological Sciences, Sam Higginbottom Institute of Agriculture, Technology and Sciences, Deemed to be University, Allahabad, India
| |
Collapse
|
|
12
|
El-Haggar SM, Mostafa TM. Cardiovascular risk in Egyptian healthy consumers of different types of combined oral contraceptives pills: A comparative study. Endocrine 2015; 49:820-7. [PMID: 25539793 DOI: 10.1007/s12020-014-0507-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Accepted: 12/05/2014] [Indexed: 12/18/2022]
Abstract
This study aimed to evaluate the associated cardiovascular risk in Egyptian healthy consumers of different types of combined oral contraceptives pills (COCPs) via determination of lipids profiles, Castelli index I, leptin, adiponectin, and resistin concentrations as cardiovascular risk factors. In this cross-sectional study, the study groups consisted of control group that represented by 30 healthy married women who were not on any contraceptive mean or any hormonal therapy and had normal menstrual cycles, group two consisted of 30 women who were users of Levonorgesterl 0.15 mg plus Ethinylestradiol 0.03 mg as 21 days cycle, group three consisted of 30 women who were users of Gestodene 0.075 mg plus Ethinylestradiol 0.03 mg as 21 days cycle, and group four consisted of 30 women who were users of Drospirenone 3 mg plus Ethinylestradiol 0.03 mg as 21 days cycle. One-way analysis of variance followed by LSD post hoc test was used for comparison of variables. P value <0.05 was considered to be significant. The comparison of the studied groups revealed that COCPs containing levonorgestrel plus ethinylestradiol resulted in significantly lower adiponectin level, and significantly higher leptin and resistin levels with more atherogenic lipid profile presented by significantly higher LDL-C, significantly lower HDL-C concentrations, and significantly higher atherogenic index. Formulation containing ethinylestradiol combined with gestodene neither altered adipose tissue function nor showed deleterious effect on lipid panel. Formulation containing ethinylestradiol combined with drospirenone resulted in significantly higher HDL-C and adiponectin concentrations. In conclusion, the uptake of COCPs containing levonorgestrel plus ethinylestradiol is associated with high cardiovascular risk since this formulation showed significantly lower adiponectin concentration, significantly higher leptin, resistin, and atherogenic index as compared to other studied groups. By contrast, the formulations containing ethinylestradiol combined with third generation progestin gestodene or fourth generation progestin drospirenone are associated with low cardiovascular risk since they neither altered adipose tissue function nor impaired lipoprotein metabolism as experienced by their favorable effect on leptin, adiponectin, and resistin, with non-changed atherogenic index, higher HDL-C levels and lower LDL-C levels as compared to levonorgestrel plus ethinylestradiol formulation.
Collapse
Affiliation(s)
- Sahar M El-Haggar
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Tanta, Egypt,
| | | |
Collapse
|
|
13
|
Ogawa H, Damrongrungruang T, Hori S, Nouno K, Minagawa K, Sato M, Miyazaki H. Effect of periodontal treatment on adipokines in type 2 diabetes. World J Diabetes 2014; 5:924-931. [PMID: 25512798 PMCID: PMC4265882 DOI: 10.4239/wjd.v5.i6.924] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 09/29/2014] [Accepted: 11/10/2014] [Indexed: 02/05/2023] Open
Abstract
The association between adipokines and inflammatory periodontal diseases has been studied over the last two decades. This review was intended to explore the observation that periodontal therapy may lead to an improvement of adipokines in diabetic patients. In summary, substantial evidence suggests that diabetes is associated with increased prevalence, extent and severity of periodontitis. Numerous mechanisms have been elucidated to explain the impact of diabetes on the periodontium. However, current knowledge concerning the role of major adipokines indicates only some of their associations with the pathogenesis of periodontitis in type 2 diabetes. Conversely, treatment of periodontal disease and reduction of oral inflammation may have positive effects on the diabetic condition, although evidence for this remains somewhat equivocal.
Collapse
|
|
14
|
Wu J, Liu Z, Meng K, Zhang L. Association of adiponectin gene (ADIPOQ) rs2241766 polymorphism with obesity in adults: a meta-analysis. PLoS One 2014; 9:e95270. [PMID: 24740426 PMCID: PMC3989273 DOI: 10.1371/journal.pone.0095270] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2013] [Accepted: 03/25/2014] [Indexed: 01/06/2023] Open
Abstract
Background Adiponectin plays an important role in regulating glucose levels and fatty acid oxidation. Multiple studies have assessed the association between rs2241766 polymorphism in the adiponectin (ADIPOQ) gene and obesity susceptibility. However, the results are inconsistent and inconclusive. The aim of this meta-analysis was to investigate this association in adults. Method Several electronic databases were searched for relevant literature published up to November 2013. Statistical analyses were performed using software Review Manager (Version 5.02) and STATA (Version 10.0). The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random-effects model or a fixed-effect model depending on heterogeneity among studies. Q tests and Egger’s tests were performed to assess heterogeneity and publication bias. Sensitivity analysis was conducted to confirm the reliability and stability of the meta-analysis. Results A total of 2,819 obese and 3,024 controls in 18 case-control studies were included in the meta-analysis. The results indicated that compared with TT genotype, the ADIPOQ-rs2241766 GG genotype was associated with an increased risk for obesity (OR = 1.39, 95% CI: 1.11–1.73, P for heterogeneity = 0.520, I2 = 0%) in overall studies. Whereas, GT genotype was associated with a borderland increased risk for obesity (OR = 1.13, 95% CI: 0.94–1.36, P for heterogeneity = 0.006, I2 = 51%). The susceptibility of obesity was increased based on genotypes of TT<GT<GG (P for trend = 0.011). Subgroup analysis of different regions revealed that the ADIPOQ-rs2241766 GG genotype increased obesity risk in the Chinese studies (OR = 1.54, 95% CI: 1.19–2.00) but not in the non-Chinese studies (OR = 1.02, 95% CI: 0.66–1.58). Similar results were observed in allelic, recessive, and dominant genetic models. There was no significant evidence of publication bias in the overall, Chinese, and non-Chinese studies (P = 0.426, P = 0.935, and P = 0.390, respectively). Conclusion The results of this meta-analysis suggest that the ADIPOQ-rs2241766 G/T polymorphism might be associated with obesity in Chinese studies but not in non-Chinese studies in adults. Better-designed studies that consider confounding factors and assess larger sample sizes with a focus on ADIPOQ-rs2241766G/T polymorphisms and obesity are required in the future.
Collapse
Affiliation(s)
- Jingjing Wu
- Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Zheng Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Kai Meng
- Department of Hospital Management, School of Health Administration and Education, Capital Medical University, Beijing, China
| | - Ling Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
- * E-mail:
| |
Collapse
|
|
15
|
Loghman M, Haghighi A, Broumand B, Ataipour Y, Tohidi M, Marzbani C, Fakharran M. Association between urinary adiponectin level and renal involvement in systemic lupus erythematous. Int J Rheum Dis 2014; 19:678-84. [PMID: 24467624 DOI: 10.1111/1756-185x.12284] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
AIM To assess association between urinary levels of adiponectin and severity of renal involvement in SLE patients. Also, this study aims to determine the value of urinary adiponectin levels to discriminate renal involvement in these patients. METHODS In a multi-center cross-sectional survey, 50 consecutive patients diagnosed as having systemic lupus erythematosus (SLE) according to American College of Rheumatology criteria were classified into two groups with or without renal involvement (microscopic hematuria, reduced glomerular filtration rate < 25% of normal value, and proteinuria > 500 mg/24 h) which was confirmed by renal biopsy. Urinary adiponectin was measured by enzyme-linked immunosorbent assay. SLE disease activity levels were assessed by SLE Disease Activity Index (SLEDAI) score. RESULTS Comparing urinary levels of adiponectin between the two groups indicated considerable discrepancy in this index between the groups with and without renal involvement (146.33 ± 258.83 ng/mL vs. 22.96 ± 44.33 ng/mL, P = 0.023). Also, urinary adiponectin/creatinine ratio was significantly higher in the former group (221.72 ± 414.58 vs. 19.99 ± 41.19, P = 0.019). Our study showed a higher mean SLEDAI score in those with renal involvement than others (23.60 ± 2.53 vs. 9.12 ± 3.03, P < 0.001). Multivariable linear regression analysis with the presence of potential confounders showed that the level of urinary adiponectin was significantly higher in those with renal involvement than other patients (β = 0.470, P = 0.023). The optimal cut-off point for urinary adiponectin levels to discriminate renal involvement from normal renal state was 7.5 ng/mL, yielding a sensitivity of 80% and specificity of 52%. CONCLUSION Urinary levels of adiponectin are significantly elevated in SLE patients with renal involvement. The measurement of this biomarker can be helpful to discriminate impaired from normal renal function in SLE patients.
Collapse
Affiliation(s)
| | | | | | | | - Maryam Tohidi
- Shahid beheshti University of Medical Sciences, Tehran, Iran
| | | | | |
Collapse
|
|
16
|
Kawaguchi-Suzuki M, Frye RF. Current clinical evidence on pioglitazone pharmacogenomics. Front Pharmacol 2013; 4:147. [PMID: 24324437 PMCID: PMC3840328 DOI: 10.3389/fphar.2013.00147] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Accepted: 11/07/2013] [Indexed: 12/31/2022] Open
Abstract
Pioglitazone is the most widely used thiazolidinedione and acts as an insulin-sensitizer through activation of the Peroxisome Proliferator-Activated Receptor-γ (PPARγ). Pioglitazone is approved for use in the management of type 2 diabetes mellitus (T2DM), but its use in other therapeutic areas is increasing due to pleiotropic effects. In this hypothesis article, the current clinical evidence on pioglitazone pharmacogenomics is summarized and related to variability in pioglitazone response. How genetic variation in the human genome affects the pharmacokinetics and pharmacodynamics of pioglitazone was examined. For pharmacodynamic effects, hypoglycemic and anti-atherosclerotic effects, risks of fracture or edema, and the increase in body mass index in response to pioglitazone based on genotype were examined. The genes CYP2C8 and PPARG are the most extensively studied to date and selected polymorphisms contribute to respective variability in pioglitazone pharmacokinetics and pharmacodynamics. We hypothesized that genetic variation in pioglitazone pathway genes contributes meaningfully to the clinically observed variability in drug response. To test the hypothesis that genetic variation in PPARG associates with variability in pioglitazone response, we conducted a meta-analysis to synthesize the currently available data on the PPARG p.Pro12Ala polymorphism. The results showed that PPARG 12Ala carriers had a more favorable change in fasting blood glucose from baseline as compared to patients with the wild-type Pro12Pro genotype (p = 0.018). Unfortunately, findings for many other genes lack replication in independent cohorts to confirm association; further studies are needed. Also, the biological functionality of these polymorphisms is unknown. Based on current evidence, we propose that pharmacogenomics may provide an important tool to individualize pioglitazone therapy and better optimize therapy in patients with T2DM or other conditions for which pioglitazone is being used.
Collapse
Affiliation(s)
- Marina Kawaguchi-Suzuki
- Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida Gainesville, FL, USA
| | | |
Collapse
|
|
17
|
Populus balsamifera Extract and Its Active Component Salicortin Reduce Obesity and Attenuate Insulin Resistance in a Diet-Induced Obese Mouse Model. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:172537. [PMID: 23781256 PMCID: PMC3678421 DOI: 10.1155/2013/172537] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/13/2013] [Accepted: 04/08/2013] [Indexed: 12/20/2022]
Abstract
Populus balsamifera L. (BP) is a medicinal plant stemming from the traditional pharmacopoeia of the Cree of Eeyou Istchee (CEI—Northern Quebec). In vitro screening studies revealed that it strongly inhibited adipogenesis in 3T3-L1 adipocytes, suggesting potential antiobesity activity. Salicortin was identified, through bioassay-guided fractionation, as the active component responsible for BP's activity. The present study aimed to assess the potential of BP and salicortin at reducing obesity and features of the metabolic syndrome, in diet-induced obese C57Bl/6 mice. Mice were subjected to high fat diet (HFD) for sixteen weeks, with BP (125 or 250 mg/kg) or salicortin (12.5 mg/kg) introduced in the HFD for the last eight of the sixteen weeks. BP and salicortin effectively reduced whole body and retroperitoneal fat pad weights, as well as hepatic triglyceride accumulation. Glycemia, insulinemia, leptin, and adiponectin levels were also improved. This was accompanied by a small yet significant reduction in food intake in animals treated with BP. BP and salicortin (slightly) also modulated key components in signaling pathways involved with glucose regulation and lipid oxidation in the liver, muscle, and adipose tissue. These results confirm the validity of the CEI pharmacopoeia as alternative and complementary antiobesity and antidiabetic therapies.
Collapse
|
|
18
|
Tsai SH, Chang EYC, Chang YC, Hee SW, Tsai YC, Chang TJ, Chuang LM. Knockdown of RyR3 enhances adiponectin expression through an atf3-dependent pathway. Endocrinology 2013; 154:1117-29. [PMID: 23389954 DOI: 10.1210/en.2012-1515] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Adiponectin is an important adipose-specific protein, which possesses insulin (INS)-sensitizing, antiinflammatory, and antiatherosclerotic functions. However, its regulation remains largely unknown. In this study, we identified that ryanodine receptor (RyR)3 plays an important role in the regulation of adiponectin expression. RyR3 was expressed in 3T3-L1 preadipocytes, and its level was decreased upon adipogenesis. Silencing of RyR3 expression in 3T3-L1 preadipocytes resulted in up-regulated adiponectin promoter activity, enhanced adiponectin mRNA expression, and more adiponectin protein secreted into the medium. An inverse relation between RyR3 and adiponectin mRNA levels was also observed in adipose tissues of db/db mice. In addition, knockdown of RyR3 with small interfering RNA (siRNA) in db/db mice and high-fat diet-fed obese mice increased serum adiponectin level, improved INS sensitivity, and lowered fasting glucose levels. These effects were in parallel with decreased mitochondrial Ca(2+), increased mitochondrial mass, and reduced activating transcription factor 3 (atf3) expression. Overexpression of atf3 in 3T3-L1 preadipocytes blocked the effect of RyR3 silencing on adiponectin expression, indicating that an atf3-dependent pathway mediates the effect downstream of RyR3 silencing. Our data suggest that RyR3 may be a new therapeutic target for improving INS sensitivity and related metabolic disorders.
Collapse
Affiliation(s)
- Shu-Huei Tsai
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100 Taiwan
| | | | | | | | | | | | | |
Collapse
|
|
19
|
Yadav A, Kataria MA, Saini V, Yadav A. Role of leptin and adiponectin in insulin resistance. Clin Chim Acta 2012; 417:80-4. [PMID: 23266767 DOI: 10.1016/j.cca.2012.12.007] [Citation(s) in RCA: 444] [Impact Index Per Article: 34.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2012] [Revised: 11/30/2012] [Accepted: 12/02/2012] [Indexed: 12/21/2022]
Abstract
Adipose tissue is a major source of energy for the human body. It is also a source of major adipocytokines adiponectin and leptin. Insulin resistance is a condition in which insulin action is impaired in adipose tissue and is more strongly linked to intra-abdominal fat than to fat in other depots. The expression of adiponectin decreases with increase in the adiposity. Adiponectin mediates insulin-sensitizing effect through binding to its receptors AdipoR1 and AdipoR2, leading to activation of adenosine monophosphate dependent kinase (AMPK), PPAR-α, and presumably other yet-unknown signalling pathways. Weight loss significantly elevates plasma adiponectin levels. Reduction of adiponectin has been associated with insulin resistance, dyslipidemia, and atherosclerosis in humans. The other major adipokine is leptin. Leptin levels increase in obesity and subcutaneous fat has been a major determinant of circulating leptin levels. The leptin signal is transmitted by the Janus kinase, signal transducer and activator of transcription ((JAK-STAT) pathway. The net action of leptin is to inhibit appetite, stimulate thermogenesis, enhance fatty acid oxidation, decrease glucose, and reduce body weight and fat.
Collapse
Affiliation(s)
- Amita Yadav
- Department of Biochemistry, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India.
| | | | | | | |
Collapse
|
|
20
|
Alkhateeb A, Al-Azzam S, Zyadine R, Abuarqoub D. Genetic association of adiponectin with type 2 diabetes in Jordanian Arab population. Gene 2012; 512:61-3. [PMID: 23041553 DOI: 10.1016/j.gene.2012.09.095] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2012] [Revised: 09/18/2012] [Accepted: 09/28/2012] [Indexed: 01/07/2023]
Abstract
Adiponectin, a protein exclusively secreted by adipose tissue and present at low levels in obese individuals, is now widely recognized as a key determinant of insulin sensitivity and protection against obesity-associated metabolic syndrome. In Jordan, prevalence of diabetes (17.1%) is twice that of the United States (7.8%). In this study, we examined the contribution of the promoter variant rs266729 (-11377C>G) of the ADIPOQ gene as a risk factor for diabetic patients in Jordan. DNA was extracted from blood samples for patients and controls .Polymerase chain reaction and restriction fragment length polymorphism were used to genotype this variant. A total of 420 type 2 diabetic patients and 230 controls were successfully genotyped. The results showed a significant genotypic (p=0.00001) and allelic (p=0.01) association with variant in the diabetic patients as compared to controls. This suggests that the ADIPOQ gene plays a major role in increasing the risk of diabetes, at least in the Jordanian Arab population.
Collapse
Affiliation(s)
- Asem Alkhateeb
- Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan.
| | | | | | | |
Collapse
|
|
21
|
González-Sánchez JL, Zabena CA, Martínez-Larrad MT, Fernández-Pérez C, Pérez-Barba M, Laakso M, Serrano-Ríos M. An SNP in the Adiponectin Gene Is Associated with Decreased Serum Adiponectin Levels and Risk for Impaired Glucose Tolerance. ACTA ACUST UNITED AC 2012; 13:807-12. [PMID: 15919831 DOI: 10.1038/oby.2005.91] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Adiponectin is a plasma protein produced by the adipose tissue. Hypoadiponectinemia has been associated with insulin resistance and several components of the metabolic syndrome (MS): type 2 diabetes, obesity, and dyslipidemia. We investigated whether single nucleotide polymorphisms (SNPs) at positions 45 and 276 in the adiponectin gene were associated with features of the MS in 747 unrelated Spanish subjects. The G allele of SNP45 and the G/G genotype of SNP276 were associated with impaired glucose tolerance (p = 0.020 and 0.042, respectively). The G/G genotype for SNP276 was associated with lower serum adiponectin levels as compared with the G/T and T/T genotypes (G/G, 10.10 +/- 0.24 microg/mL; G/T, 10.98 +/- 0.32 microg/mL; T/T, 12.00 +/- 0.92 microg/mL; p = 0.015) even after adjustment for sex, age, BMI, waist-to-hip ratio, homeostasis model assessment index, and the degree of glucose tolerance (p = 0.040). We found a significant negative association of circulating adiponectin levels with waist-to-hip ratio (r = -0.42, p < 0.001), sagittal abdominal diameter (r = -0.24, p < 0.001), triglycerides (r = -0.32, p < 0.001), homeostasis model assessment index (r = -0.14, p = 0.001), and uric acid (r = -0.36, p < 0.001) and positive association with high-density lipoprotein-cholesterol (r = 0.41, p < 0.001). Our findings indicate that serum adiponectin levels are associated with several components of the MS. The SNP276 of the adiponectin gene may affect impaired glucose tolerance and hypoadiponectinemia.
Collapse
|
|
22
|
Mtiraoui N, Ezzidi I, Turki A, Chaieb A, Mahjoub T, Almawi WY. Single-nucleotide polymorphisms and haplotypes in the adiponectin gene contribute to the genetic risk for type 2 diabetes in Tunisian Arabs. Diabetes Res Clin Pract 2012; 97:290-7. [PMID: 22497971 DOI: 10.1016/j.diabres.2012.02.015] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2011] [Revised: 02/14/2012] [Accepted: 02/21/2012] [Indexed: 12/29/2022]
Abstract
Adiponectin is an adipocyte-produced protein involved in regulating glucose, lipid, and energy metabolism, and is encoded by ADIPOQ (APM1) gene. ADIPOQ polymorphisms were previously associated with type 2 diabetes (T2DM) in Caucasian and non-Caucasian populations. We investigated the contribution of 13 polymorphisms in the promoter, coding regions, and 3'untranslated region of ADIPOQ gene to T2DM in 917 patients and 748 normoglycemic control subjects. ADIPOQ genotyping was done by allelic discrimination method. Of the 13 ADIPOQ variants analyzed, higher minor allele frequency of rs16861194 (P<0.001), rs17300539 (P<0.001), rs266729 (P<0.001), rs822396 (P=0.02), rs2241767 (P=0.03), and rs1063538 (P=0.02) were seen in T2DM cases. Varied association of ADIPOQ genotypes with T2DM was seen according to the genetic model used: rs17300539 and rs266729 were significantly associated with T2DM under the three models, while rs16861194 was association with T2DM under additive and dominant models, and rs822396, rs2241766, and rs1063538 were associated with T2DM under the dominant models only. Haploview analysis revealed low linkage disequilibrium between the ADIPOQ variants, resulting in high haplotype diversity, and two blocks were identified, each differentially associated with T2DM. These results support a significant association of ADIPOQ gene polymorphism with T2DM in Tunisian Arabs.
Collapse
Affiliation(s)
- Nabil Mtiraoui
- Research Unit of Biology and Genetics of Cancer and Haematological and Autoimmune diseases, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia
| | | | | | | | | | | |
Collapse
|
|
23
|
Keku TO, Vidal A, Oliver S, Hoyo C, Hall IJ, Omofoye O, McDoom M, Worley K, Galanko J, Sandler RS, Millikan R. Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites. Cancer Causes Control 2012; 23:1127-38. [PMID: 22565227 DOI: 10.1007/s10552-012-9981-2] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2011] [Accepted: 04/23/2012] [Indexed: 01/29/2023]
Abstract
PURPOSE Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)( n ) repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor-binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study. METHODS Participants were African Americans (231 cases and 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5'-exonuclease (Taqman) assay. The IGF-I (CA)(n) repeat was assayed by PCR and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by logistic regression. RESULTS The IGF-I (CA)( 19 ) repeat was higher in White controls (50 %) than African American controls (31 %). Whites homozygous for the IGF-I (CA)(19) repeat had a nearly twofold increase in risk of colon cancer (OR = 1.77; 95 % CI = 1.15-2.73), but not African Americans (OR = 0.73, 95 % CI 0.50-1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR = 0.49, 95 % CI 0.28-0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p-trend <0.05). CONCLUSIONS These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans.
Collapse
Affiliation(s)
- Temitope O Keku
- Department of Medicine, Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, 27599-7032, USA.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
24
|
Yoon JH, Kim J, Song P, Lee TG, Suh PG, Ryu SH. Secretomics for skeletal muscle cells: a discovery of novel regulators? Adv Biol Regul 2012; 52:340-350. [PMID: 22781747 DOI: 10.1016/j.jbior.2012.03.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2012] [Revised: 03/20/2012] [Accepted: 03/20/2012] [Indexed: 06/01/2023]
Abstract
Metabolic tissues, including skeletal muscle, adipose tissue and the digestive system, dynamically secrete various factors depending on the metabolic state, communicate with each other and orchestrate functions to maintain body homeostasis. Skeletal muscle secretes cytokines such as interleukin-6 (IL-6), IL-15, fibroblast growth factor-21 (FGF21) and IL-8. These compounds, myokines, play important roles in biological homeostasis such as energy metabolism, angiogenesis and myogenesis. New technological advances have allowed secretomics - analysis of the secretome - to be performed. The application of highly sensitive mass spectrometry makes qualitative and quantitative analysis of the secretome of skeletal muscle possible. Secretory proteins derived from skeletal muscle cells under various conditions were analyzed, and many important factors were suggested. In-depth studies of the secretome from metabolic cells in various conditions are strongly recommended. This study will provide information on methods of novel communication between metabolic tissues.
Collapse
Affiliation(s)
- Jong Hyuk Yoon
- Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk 790-784, Republic of Korea
| | | | | | | | | | | |
Collapse
|
|
25
|
Inflammation and oxidative stress in obesity-related glomerulopathy. Int J Nephrol 2012; 2012:608397. [PMID: 22567283 PMCID: PMC3332212 DOI: 10.1155/2012/608397] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2011] [Accepted: 02/06/2012] [Indexed: 01/17/2023] Open
Abstract
Obesity-related glomerulopathy is an increasing cause of end-stage renal disease. Obesity has been considered a state of chronic low-grade systemic inflammation and chronic oxidative stress. Augmented inflammation in adipose and kidney tissues promotes the progression of kidney damage in obesity. Adipose tissue, which is accumulated in obesity, is a key endocrine organ that produces multiple biologically active molecules, including leptin, adiponectin, resistin, that affect inflammation, and subsequent deregulation of cell function in renal glomeruli that leads to pathological changes. Oxidative stress is also associated with obesity-related renal diseases and may trigger the initiation or progression of renal damage in obesity. In this paper, we focus on inflammation and oxidative stress in the progression of obesity-related glomerulopathy and possible interventions to prevent kidney injury in obesity.
Collapse
|
|
26
|
Saxena M, Srivastava N, Banerjee M. Genetic association of adiponectin gene polymorphisms (+45T/G and +10211T/G) with type 2 diabetes in North Indians. Diabetes Metab Syndr 2012; 6:65-69. [PMID: 23153972 DOI: 10.1016/j.dsx.2012.08.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Adiponectin (ADIPOQ) is an abundant protein hormone which belongs to a family of so-called adipokines. It is expressed mostly by adipocytes and is an important regulator of lipid and glucose metabolism. It was shown that decreased serum adiponectin concentration indicated insulin resistance and type 2 diabetes (T2DM) with the risk of cardiovascular complications. The fact that adiponectin is an insulin-sensitizing hormone with anti-diabetic, anti-inflammatory and anti-atherogenic properties, we proposed to study the association of ADIPOQ gene polymorphisms in subjects with T2DM. DNA was isolated from venous blood samples, quantified and subjected to Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) using suitable primers and restriction endonucleases. Adiponectin levels were measured in serum using ELISA. The genotypic, allelic and carriage rate frequencies distribution in patients and controls were analyzed by PSAW software (ver. 17.0). Odd ratios (OR) with 95% confidence interval (CI) were determined to describe the strength of association by logistic regression model. Out of the two polymorphisms studied, +10211T/G showed significant association (P=0.042), the 'G' allele association being highly significant (P=0.022). Further analysis showed that individuals with 'GG' haplotype were at increased risk of T2DM up to 15.5 times [P=0.015, OR (95% CI); 15.558 (1.690-143.174)]. The present study showed that the 'G' allele of ADIPOQ gene (+10211T/G) plays a prominent role with respect to T2DM susceptibility in North-Indian population.
Collapse
Affiliation(s)
- Madhukar Saxena
- Molecular & Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow, India.
| | | | | |
Collapse
|
|
27
|
Tsuzaki K, Kotani K, Sano Y, Fujiwara S, Gazi IF, Elisaf M, Sakane N. The relationship between adiponectin, an adiponectin gene polymorphism, and high-density lipoprotein particle size: from the Mima study. Metabolism 2012; 61:17-21. [PMID: 21820140 DOI: 10.1016/j.metabol.2011.06.021] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2011] [Revised: 06/24/2011] [Accepted: 06/24/2011] [Indexed: 01/06/2023]
Abstract
This study examined the association among serum adiponectin levels, a single nucleotide polymorphism (SNP) of the adiponectin gene, and the size of serum high-density lipoprotein (HDL) particles in a general population. A total of 275 subjects were examined as part of the community-based Mima study. Serum adiponectin levels were measured with an enzyme-linked immunosorbent assay. Serum small-sized HDL was measured with the electrophoretic separation of lipoproteins using the Lipoprint system. Single nucleotide polymorphism G276T (rs1501299, SNP276) of the adiponectin gene was determined with a fluorescent allele-specific DNA primer assay system. Age- and sex-adjusted correlation test revealed a significant inverse relationship between small-sized HDL and adiponectin levels (r = -0.236, P < .001). More percentages of small-sized HDL were observed in the subjects with the SNP276 G/G and G/T genotypes than in those with the T/T genotype (5.5% ± 5.0% vs 3.0% ± 2.9%, P = .016). In a multiple regression analysis, small-sized HDL was significantly and independently correlated with triglycerides levels (β = 0.133, P = .030), adiponectin levels (β = -0.242, P < .001), and the SNP276 G allele (β = -0.142, P = .014). Our findings indicated that adiponectin and SNP276 of the adiponectin gene may modify the size of HDL particles.
Collapse
Affiliation(s)
- Kokoro Tsuzaki
- Division of Preventive Medicine and Diabetes Education, Clinical Research Institute for Endocrine and Metabolic Disease, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | | | | | | | | | | | | |
Collapse
|
|
28
|
Fallah S, Sanjary Pour M, Rabbani Chadegani A, Korani M. Adiponectin, leptin and lipid profiles evaluation in oral contraceptive pill consumers. Arch Gynecol Obstet 2011; 285:1747-52. [DOI: 10.1007/s00404-011-2192-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2011] [Accepted: 12/16/2011] [Indexed: 10/14/2022]
|
|
29
|
Abstract
Even though there have been major advances in therapy, atherosclerosis and coronary artery disease retain their lead as one of the major causes of morbidity and mortality in the first decade of 21(st) century. To add to the woes, we have diabetes, obesity and insulin resistance as the other causes. The adipose tissue secretes several bioactive mediators that influence inflammation, insulin resistance, diabetes, atherosclerosis and several other pathologic states besides the regulation of body weight. These mediators are mostly proteins and are termed "adipocytokines". Adiponectin, resistin, visfatin, retinol binding protein-4 (RBP-4) and leptin are a few such proteins. Adiponectin is a multimeric protein, acting via its identified receptors, AdipoR1 and AdipoR2. It is a potential biomarker for metabolic syndrome and has several antiinflammatory actions. Adiponectin increases insulin sensitivity and ameliorates obesity. Resistin, another protein secreted by the adipose tissue, derived its name due to its involvement in the development of insulin resistance. It plays a role in the pathophysiology of several conditions because of its robust proinflammatory activity mediated through the activation of extracellular signal regulated kinases 1 and 2 (ERK 1/2). In 2007, resistin was reported to have protective effect in ischemia-reperfusion injury and myocyte-apoptosis in the setting of myocardial infarction (MI). RBP-4 is involved in the developmental pathology of type 2 diabetes mellitus and obesity. Visfatin has been described as an inflammatory cytokine. Increased expression of visfatin mRNA has been observed in inflammatory conditions like atherosclerosis and inflammatory bowel disease. Leptin mainly regulates the food intake and energy homeostasis. Leptin resistance has been associated with development of obesity and insulin resistance. Few drugs (thiazolidinediones, rimonabant, statins, etc.) and some lifestyle modifications have been found to improve the levels of adipocytokines. Their role in therapy has a lot in store to be explored upon.
Collapse
Affiliation(s)
- Hardik Gandhi
- Department of Pharmacy, Faculty of Technology and Engineering, The M. S. University of Baroda, Vadodara - 390 001, Gujarat, India
| | | | | |
Collapse
|
|
30
|
Breast milk hormones and regulation of glucose homeostasis. Int J Pediatr 2011; 2011:803985. [PMID: 21760816 PMCID: PMC3133796 DOI: 10.1155/2011/803985] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2010] [Accepted: 02/28/2011] [Indexed: 01/22/2023] Open
Abstract
Growing evidence suggests that a complex relationship exists between the central nervous system and peripheral organs involved in energy homeostasis. It consists in the balance between food intake and energy expenditure and includes the regulation of nutrient levels in storage organs, as well as in blood, in particular blood glucose. Therefore, food intake, energy expenditure, and glucose homeostasis are strictly connected to each other. Several hormones, such as leptin, adiponectin, resistin, and ghrelin, are involved in this complex regulation. These hormones play a role in the regulation of glucose metabolism and are involved in the development of obesity, diabetes, and metabolic syndrome. Recently, their presence in breast milk has been detected, suggesting that they may be involved in the regulation of growth in early infancy and could influence the programming of energy balance later in life. This paper focuses on hormones present in breast milk and their role in glucose homeostasis.
Collapse
|
|
31
|
Adiponectin gene polymorphism and its association with type 2 diabetes mellitus. Indian J Clin Biochem 2011; 26:172-7. [PMID: 22468045 DOI: 10.1007/s12291-011-0123-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2010] [Accepted: 02/07/2011] [Indexed: 10/18/2022]
Abstract
Mutations in different regions of adiponectin gene have been reported to be associated with obesity, atherosclerosis and type 2 diabetes mellitus. The present study was aimed to investigate the association among SNP 45 T > G of adiponectin gene and type 2 diabetes in South Indian population. 75 clinically diagnosed case of type 2 diabetes were studied and compared with 75 apparently healthy controls. The genotype frequency of SNP45 T > G in exon 2 of adiponectin gene was determined by PCR based restriction enzyme analysis using the restriction enzyme SmaI. (recognition site: CCC↓GGG). Three kind of genotypes: wild type TT (470 bp), heterozygous type TG (470 bp, 336 bp, 134 bp) and homozygote mutant type GG (336 bp, 134 bp) were studied. A positive association has been found between SNP45 T > G and type 2 diabetes in the study population (P = 0.010, OR = 3.797, 95% CI = 1.312-10.983). Therefore, SNP45T > G in adiponectin gene may be one of the risk factors for type 2 diabetes.
Collapse
|
|
32
|
Bonnefond A, Froguel P, Vaxillaire M. The emerging genetics of type 2 diabetes. Trends Mol Med 2010; 16:407-16. [PMID: 20728409 DOI: 10.1016/j.molmed.2010.06.004] [Citation(s) in RCA: 111] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2010] [Accepted: 06/30/2010] [Indexed: 12/16/2022]
Abstract
The elucidation of several genetic etiologies of both monogenic and polygenic type 2 diabetes (T2D) has revealed several key regulators of glucose homeostasis and insulin secretion in humans. Genome-wide association studies (GWAS) have been instrumental in most of these recent discoveries. The T2D susceptibility genes identified so far are mainly involved in pancreatic beta-cell maturation or function. However, common DNA variants in those genes only explain approximately 10% of T2D heritability. The resequencing of whole exomes and whole genomes with next-generation technologies should identify additional genetic changes that contribute to the monogenic forms of diabetes and possibly provide novel clues to the genetic architecture of common adult T2D.
Collapse
|
|
33
|
Abstract
It has been suggested that a more precise selection of predictive biomarkers may prove useful in the early diagnosis of type 2 diabetes (T2D), even when glucose tolerance is normal. This is vital since many T2D cases may be preventable by avoiding those factors that trigger the disease process (primary prevention) or by use of therapy that modulates the disease process before the onset of clinical symptoms (secondary prevention) occurs. The selection of predictive markers must be carefully assessed and depends mainly on three important parameters: sensitivity, specificity and positive predictive value. Unfortunately, biomarkers with ideal specificity and sensitivity are difficult to find. One potential solution is to use the combinatorial power of different biomarkers, each of which alone may not offer satisfactory specificity and sensitivity. Recent technological advances in proteomics and bioinformatics offer a great opportunity for the discovery of different potential predictive markers. In this review, we described a cellular T2D model as an example with the intent of providing specific enrichment and new identification strategies, which might have the potential to improve predictive biomarker identification and to bring accuracy in disease diagnosis and classification, as well as therapeutic monitoring in the early phase of T2D.
Collapse
|
|
34
|
Vendramini MF, Pereira AC, Ferreira SR, Kasamatsu TS, Moisés RS. Association of genetic variants in the adiponectin encoding gene (ADIPOQ) with type 2 diabetes in Japanese Brazilians. J Diabetes Complications 2010; 24:115-20. [PMID: 19269196 DOI: 10.1016/j.jdiacomp.2009.01.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2008] [Revised: 01/10/2009] [Accepted: 01/21/2009] [Indexed: 01/02/2023]
Abstract
AIM The objective of this study is to assess the contribution of ADIPOQ variants to type 2 diabetes in Japanese Brazilians. METHODS We genotyped 200 patients with diabetes mellitus (100 male and 100 female, aged 55.0 years [47.5-64.0 years]) and 200 control subjects with normal glucose tolerant (NGT) (72 male and 128 female, aged 52.0 years [43.5-64.5 years]). RESULTS Whereas each polymorphism studied (T45G, G276T, and A349G) was not significantly associated with type 2 diabetes mellitus, the haplotype GGA was overrepresented in our diabetic population (9.3% against 3.1% in NGT individuals, P=.0003). Also, this haplotype was associated with decreased levels of adiponectin. We also identified three mutations in exon 3: I164T, R221S, and H241P, but, owing to the low frequencies of them, associations with type 2 diabetes could not be evaluated. The subjects carrying the R221S mutation had plasma adiponectin levels lower than those without the mutation (2.10 microg/ml [1.35-2.55 microg/ml] vs. 6.68 microg/ml [3.90-11.23 microg/ml], P=.015). Similarly, the I164T mutation carriers had mean plasma adiponectin levels lower than those noncarriers (3.73 microg/ml [3.10-4.35 microg/ml] vs. 6.68 microg/ml [3.90-11.23 microg/ml]), but this difference was not significant (P=.17). CONCLUSIONS We identified in the ADIPOQ gene a risk haplotype for type 2 diabetes in the Japanese Brazilian population.
Collapse
Affiliation(s)
- Marcio F Vendramini
- Division of Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, SP, Brazil
| | | | | | | | | |
Collapse
|
|
35
|
Mazaki-Tovi S, Romero R, Vaisbuch E, Erez O, Mittal P, Chaiworapongsa T, Kim SK, Pacora P, Yeo L, Gotsch F, Dong Z, Yoon BH, Hassan SS, Kusanovic JP. Maternal serum adiponectin multimers in gestational diabetes. J Perinat Med 2009. [PMID: 19530957 DOI: 10.1515/jpm.2009.101.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Adiponectin, an adipokine with profound insulin-sensitizing effect, consists of heterogeneous species of multimers. These oligomeric complexes circulate as low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms and can exert differential biological effects. The aims of this study were to determine whether there is a change in circulating adiponectin multimers in the presence of gestational diabetes mellitus (GDM), overweight/obesity or with a treatment with sulfonylurea or insulin in patients with GDM. STUDY DESIGN This cross-sectional study included women with: 1) normal pregnancy (n=149); and 2) patients with GDM (n=72). Thirty-three patients with GDM were managed with diet alone. Among the others 39 diabetic patients, 17 were treated with Glyburide and 22 with insulin. The study population was further stratified by first trimester body mass index (BMI) (normal weight <25 kg/m(2) vs. overweight/obese > or =25 kg/m(2)). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. RESULTS 1) The median maternal serum of total, HMW, MMW and LMW were lower in patients with GDM than in those with normal pregnancies (P<0.001 for all comparisons); 2) patients with GDM had a lower HMW/total adiponectin ratio and a higher MMW/total and LMW/total adiponectin ratio than those with a normal pregnancy (P<0.001 for all comparisons); and 3) among GDM patients, there were no differences in the concentrations and relative distribution of adiponectin multimers between those who were managed with diet, and those who were treated with pharmacological agents. CONCLUSION 1) GDM is characterized by a distinctive pattern of concentrations and relative distribution of adiponectin multimers akin to Type 2 diabetes mellitus; 2) dysregulation of adiponectin multimeres can provide a mechanistic basis for the association between adiposity and GDM.
Collapse
Affiliation(s)
- Shali Mazaki-Tovi
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women's Hospital, Detroit, MI 48201, USA
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Tsuzaki K, Kotani K, Nagai N, Saiga K, Sano Y, Hamada T, Moritani T, Yoshimura M, Egawa K, Horikawa C, Kitagawa Y, Kiso Y, Sakane N. Adiponectin gene single-nucleotide polymorphisms and treatment response to obesity. J Endocrinol Invest 2009; 32:395-400. [PMID: 19794286 DOI: 10.1007/bf03346474] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND In the adiponectin gene polymorphisms, single-nucleotide polymorphism (SNP)-45 and SNP276 have reportedly been associated with obesity, Type 2 diabetes, and other features of metabolic syndrome. AIM Whether these adiponectin SNP affect obesity-related parameters during caloric restriction in obese subjects. SUBJECTS AND METHODS Thirty- two obese Japanese women were treated by meal replacement with a low calorie diet for 8 weeks and asked to maintain their habitual lifestyle. Obesity-related parameters were measured before and after the treatment period. We determined four SNP (T45G, I164T, G276T, and C-11377G) using a fluorescent allele-specific DNA primer assay systemand FRET probe assay system. RESULTS After the treatment, the extent of decrease in waist circumference was greater in the subjects with the G/G or G/T genotype of SNP276 than in those with the T/T genotype (p=0.026). As for SNP45, the extent of decrease in triglyceride levels was greater in the subjects with the T/T genotype than in those with the T/G genotype (p=0.003). For SNP-11377, the extent of decrease in systolic blood pressure and fasting plasma glucose was greater in the subjects with the C/G or G/G genotype than in those with the C/C genotype (p=0.044). CONCLUSION Our findings indicate that each SNP in the adiponectin gene might modify the change in obesity-related parameters during meal replacement with a low calorie diet.
Collapse
Affiliation(s)
- K Tsuzaki
- Division of Preventive Medicine and Diabetes Education, Clinical Research Institute for Endocrine and Metabolic Disease, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
37
|
Mazaki-Tovi S, Romero R, Vaisbuch E, Erez O, Mittal P, Chaiworapongsa T, Kim SK, Pacora P, Yeo L, Gotsch F, Dong Z, Yoon BH, Hassan SS, Kusanovic JP. Maternal serum adiponectin multimers in gestational diabetes. J Perinat Med 2009; 37:637-50. [PMID: 19530957 PMCID: PMC3593069 DOI: 10.1515/jpm.2009.101] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
OBJECTIVE Adiponectin, an adipokine with profound insulin-sensitizing effect, consists of heterogeneous species of multimers. These oligomeric complexes circulate as low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms and can exert differential biological effects. The aims of this study were to determine whether there is a change in circulating adiponectin multimers in the presence of gestational diabetes mellitus (GDM), overweight/obesity or with a treatment with sulfonylurea or insulin in patients with GDM. STUDY DESIGN This cross-sectional study included women with: 1) normal pregnancy (n=149); and 2) patients with GDM (n=72). Thirty-three patients with GDM were managed with diet alone. Among the others 39 diabetic patients, 17 were treated with Glyburide and 22 with insulin. The study population was further stratified by first trimester body mass index (BMI) (normal weight <25 kg/m(2) vs. overweight/obese > or =25 kg/m(2)). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. RESULTS 1) The median maternal serum of total, HMW, MMW and LMW were lower in patients with GDM than in those with normal pregnancies (P<0.001 for all comparisons); 2) patients with GDM had a lower HMW/total adiponectin ratio and a higher MMW/total and LMW/total adiponectin ratio than those with a normal pregnancy (P<0.001 for all comparisons); and 3) among GDM patients, there were no differences in the concentrations and relative distribution of adiponectin multimers between those who were managed with diet, and those who were treated with pharmacological agents. CONCLUSION 1) GDM is characterized by a distinctive pattern of concentrations and relative distribution of adiponectin multimers akin to Type 2 diabetes mellitus; 2) dysregulation of adiponectin multimeres can provide a mechanistic basis for the association between adiposity and GDM.
Collapse
Affiliation(s)
- Shali Mazaki-Tovi
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| | - Roberto Romero
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
| | - Edi Vaisbuch
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| | - Offer Erez
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| | - Pooja Mittal
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| | - Tinnakorn Chaiworapongsa
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| | - Sun Kwon Kim
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
| | - Percy Pacora
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
| | - Lami Yeo
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| | - Francesca Gotsch
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
| | - Zhong Dong
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
| | - Bo Hyun Yoon
- Department of Obstetrics and Gynecology, Seoul National University, Seoul, Korea
| | - Sonia S. Hassan
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| | - Juan Pedro Kusanovic
- Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women’s Hospital, Bethesda, MD, and Detroit, MI
- Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, Detroit, MI
| |
Collapse
|
|
38
|
A new frame in thromboembolic cardiovascular disease: Adipocytokine. Int J Cardiol 2008; 139:100-2. [PMID: 18723235 DOI: 10.1016/j.ijcard.2008.06.082] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2008] [Accepted: 06/28/2008] [Indexed: 11/24/2022]
Abstract
Recent researches have shown that adipocytokines secreted by adipose tissue play an important role in inflammation which is considered to be a crucial step in the pathogenesis of atherosclerosis. Leptin, one of the earlier adipocytokines, is known to play a major role in cardiovascular disease and recent observations suggest that leptin is an independent risk factor for coronary heart disease. Resistin, another recently discovered adipocytokine, has been related to risk factors of atherosclerosis, and in diabetic individuals serum resistin levels correlate well with inflammatory markers and are predictive for the development of cardiovascular disease. Adiponectin, another adipocytokine of interest in recent years, seems to be the most promising one studied to date. In contrast to leptin and resistin, adiponectin seems to be beneficial for health and it is a protective factor and decreased in obesity. However, many other factors derived from adipose tissue have also been discovered, such as interleukin-6, tumor necrosis factor alpha, monocyte chemoattractant protein 1, apelin, visfatin and probably others awaiting discovery in the near future. In this paper, we discussed the role of adipocytokines in the pathogenesis of atherosclerotic cardiovascular disease.
Collapse
|
|
39
|
Vimaleswaran KS, Radha V, Ramya K, Babu HNS, Savitha N, Roopa V, Monalisa D, Deepa R, Ghosh S, Majumder PP, Rao MRS, Mohan V. A novel association of a polymorphism in the first intron of adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia in Asian Indians. Hum Genet 2008; 123:599-605. [PMID: 18465144 DOI: 10.1007/s00439-008-0506-8] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2008] [Accepted: 04/28/2008] [Indexed: 12/17/2022]
Abstract
Adiponectin is an adipose tissue specific protein that is decreased in subjects with obesity and type 2 diabetes. The objective of the present study was to examine whether variants in the regulatory regions of the adiponectin gene contribute to type 2 diabetes in Asian Indians. The study comprised of 2,000 normal glucose tolerant (NGT) and 2,000 type 2 diabetic, unrelated subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Fasting serum adiponectin levels were measured by radioimmunoassay. We identified two proximal promoter SNPs (-11377C-->G and -11282T-->C), one intronic SNP (+10211T-->G) and one exonic SNP (+45T-->G) by SSCP and direct sequencing in a pilot study (n = 500). The +10211T-->G SNP alone was genotyped using PCR-RFLP in 4,000 study subjects. Logistic regression analysis revealed that subjects with TG genotype of +10211T-->G had significantly higher risk for diabetes compared to TT genotype [Odds ratio 1.28; 95% Confidence Interval (CI) 1.07-1.54; P = 0.008]. However, no association with diabetes was observed with GG genotype (P = 0.22). Stratification of the study subjects based on BMI showed that the odds ratio for obesity for the TG genotype was 1.53 (95%CI 1.3-1.8; P < 10(-7)) and that for GG genotype, 2.10 (95% CI 1.3-3.3; P = 0.002). Among NGT subjects, the mean serum adiponectin levels were significantly lower among the GG (P = 0.007) and TG (P = 0.001) genotypes compared to TT genotype. Among Asian Indians there is an association of +10211T-->G polymorphism in the first intron of the adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia.
Collapse
Affiliation(s)
- Karani S Vimaleswaran
- Madras Diabetes Research Foundation, Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Diabetes and ICMR Advanced Centre for Genomics of Diabetes, Chennai, India
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Ukkola O, Terán-García M, Tremblay A, Després JP, Bouchard C. Adiponectin concentration and insulin indicators following overfeeding in identical twins. J Endocrinol Invest 2008; 31:132-7. [PMID: 18362504 DOI: 10.1007/bf03345579] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
UNLABELLED Low adiponectin levels have been associated with high body mass index, low insulin sensitivity, and diabetes. OBJECTIVE To assess the relationships between changes in serum adiponectin concentration and adiposity, glucose, and insulin in response to long-term overfeeding in identical twins and to calculate the twin resemblance in serum adiponectin concentrations. SUBJECTS AND DESIGN Twenty-four sedentary young men [mean (+/-SD) age, 21+/-2 yr] who constituted 12 pairs of healthy identical twins were studied for metabolic and adiponectin changes in response to overfeeding. INTERVENTION Subjects were overfed by 84,000 kcal over a 100-day period. OUTCOME MEASURES The overfeeding study provides an opportunity to examine the relationships between adiponectin and changes in body weight, adiposity, plasma glucose and insulin. RESULTS Serum adiponectin concentration correlated positively with body weight (r= 0.41, p=0.05) at baseline but not with indicators of adiposity or with visceral fat. No relationship existed between baseline adiponectin concentration and body weight or adiposity gains with overfeeding. However, serum adiponectin decreased significantly by -2.35+/-0.48 microg/ml (p=0.001) in response to overfeeding. Baseline adiponectin levels correlated negatively with changes in plasma fasting glucose levels (r=-0.53, p=0.01) and homeostasis model assessment index (r=-0.41, p=0.05), independently of fat mass. The intrapair coefficient for twin resemblance (r=0.75, p=0.001) strongly suggests that baseline serum adiponectin concentration is a familial trait. CONCLUSIONS These data provide evidence that adiponectin concentration is a familial trait in normal-weight individuals, that it decreases when challenged by positive energy balance, and that its overfeeding-induced variations are correlated with glucose and insulin levels.
Collapse
Affiliation(s)
- O Ukkola
- Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
| | | | | | | | | |
Collapse
|
|
41
|
Chavez-Tapia NC, Sanchez-Avila F, Vasquez-Fernandez F, Torres-Machorro A, Tellez-Avila FI, Uribe M. Non-alcoholic fatty-liver disease in pediatric populations. J Pediatr Endocrinol Metab 2007; 20:1059-73. [PMID: 18051925 DOI: 10.1515/jpem.2007.20.10.1059] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The increasing prevalence of obesity is not only observed in adults. Children are affected by obesity and related diseases, such as chronic liver disease, more frequently than in the past. Nonalcoholic fatty-liver disease is an important cause of chronic liver disease and in the near future will become important worldwide. Considering this phenomenon, it is important for gastroenterologists and hepatologists to be aware of the presence of nonalcoholic fatty-liver disease in pediatric populations and to treat it adequately. This practice will have important benefits for future generations. This review discusses the most important aspects in epidemiology, diagnostics and treatment of nonalcoholic fatty-liver disease in children.
Collapse
Affiliation(s)
- Norberto C Chavez-Tapia
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, Mexico City, Mexico.
| | | | | | | | | | | |
Collapse
|
|
42
|
Rothenbacher D, Nieters A, Weyermann M, Brenner H. Adiponectin polymorphisms, cord blood levels of adiponectin, and body composition. J Allergy Clin Immunol 2007; 120:469-70. [PMID: 17498788 DOI: 10.1016/j.jaci.2007.03.036] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2006] [Revised: 03/23/2007] [Accepted: 03/26/2007] [Indexed: 12/31/2022]
|
|
43
|
Abstract
Diabetes mellitus is widely recognized as one of the leading causes of death and disability. While insulin insensitivity is an early phenomenon partly related to obesity, pancreatic beta-cell function declines gradually over time even before the onset of clinical hyperglycemia. Several mechanisms have been proposed to be responsible for insulin resistance, including increased non-esterified fatty acids, inflammatory cytokines, adipokines, and mitochondrial dysfunction, as well as glucotoxicity, lipotoxicity, and amyloid formation for beta-cell dysfunction. Moreover, the disease has a strong genetic component, although only a handful of genes have been identified so far. Diabetic management includes diet, exercise and combinations of antihyperglycemic drug treatment with lipid-lowering, antihypertensive, and antiplatelet therapy. Since many persons with type 2 diabetes are insulin resistant and overweight, nutrition therapy often begins with lifestyle strategies to reduce energy intake and increase energy expenditure through physical activity. These strategies should be implemented as soon as diabetes or impaired glucose homoeostasis (pre-diabetes) is diagnosed.
Collapse
Affiliation(s)
- George V Z Dedoussis
- Department of Nutrition and Dietetics, Harokopio University of Athens, 70 El. Venizelou Str., 17671 Kallithea-Athens, Greece
| | | | | |
Collapse
|
|
44
|
Walley AJ, Blakemore AIF, Froguel P. Genetics of obesity and the prediction of risk for health. Hum Mol Genet 2006; 15 Spec No 2:R124-30. [PMID: 16987875 DOI: 10.1093/hmg/ddl215] [Citation(s) in RCA: 103] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Obesity has always existed in human populations, but until very recently was comparatively rare. The availability of abundant, energy-rich processed foods in the last few decades has, however, resulted in a sharp rise in the prevalence of obesity in westernized countries. Although it is the obesogenic environment that has resulted in this major healthcare problem, it is acting by revealing a sub-population with a pre-existing genetic predisposition to excess adiposity. There is substantial evidence for the heritability of obesity, and research in both rare and common forms of obesity has identified genes with significant roles in its aetiology. Application of this understanding to patient care has been slower. Until very recently, the health risks of obesity were thought to be well understood, with a straightforward correlation between increasing obesity and increasing risk of health problems such as type 2 diabetes, coronary heart disease, hypertension, arthritis and cancer. It is becoming clear, however, that the location of fat deposition, variation in the secretion of adipokines and other factors govern whether a particular obese person develops such complications. Prediction of the health risks of obesity for individual patients is not straightforward, but continuing advances in understanding of genetic factors influencing obesity risk and improved diagnostic technologies mean that the future for such prediction is looking increasingly bright.
Collapse
Affiliation(s)
- Andrew J Walley
- Section of Genomic Medicine, Division of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
| | | | | |
Collapse
|
|
45
|
Schreiber JE, Singh NK, Shermak MA. The effect of liposuction and diet on ghrelin, adiponectin, and leptin levels in obese Zucker rats. Plast Reconstr Surg 2006; 117:1829-35. [PMID: 16651955 DOI: 10.1097/01.prs.0000209966.11255.4f] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND The fat-regulating hormones, adiponectin, ghrelin, and leptin, have been studied extensively with the hope that some therapeutic modality might be gleaned from their augmentation or blockade. The authors studied levels of ghrelin, adiponectin, and leptin after liposuction in obese male Zucker rats. In addition, they altered the fat and carbohydrate content of the rats' postoperative diets to determine whether diet affects hormonal levels and/or liposuction outcome. METHODS Thirty-five male, obese Zucker rats were divided into four experimental groups. Group I (n = 10) was fed a low-fat/low-carbohydrate diet; group II (n = 10) was fed a regular chow diet; and group III (n = 10) was fed a high-fat/high-carbohydrate diet. Five additional rats served as the baseline, unoperated group. The experimental rats underwent subcutaneous liposuction, and for 6 weeks they were then fed their experimental diets starting on day 0. Experimental rats were euthanized on day 42 and blood was sampled for hormonal, triglyceride, and cholesterol levels. RESULTS Triglyceride levels were significantly higher in the high-fat/high-carbohydrate group compared with the regular chow and low-fat/low-carbohydrate groups, indicating an effect of diet on systemic circulation after liposuction. Ghrelin levels decreased significantly and leptin levels demonstrated an increasing trend after liposuction. Adiponectin levels did not demonstrate any change with alteration in diet or liposuction. CONCLUSIONS Liposuction may prove to offer patients medically therapeutic benefits through hormonal alterations. After liposuction, diet plays an important role in weight gain.
Collapse
Affiliation(s)
- Jeffrey E Schreiber
- Division of Plastic Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | | | | |
Collapse
|
|
46
|
|
|
47
|
Vaxillaire M, Dechaume A, Vasseur-Delannoy V, Lahmidi S, Vatin V, Leprêtre F, Boutin P, Hercberg S, Charpentier G, Dina C, Froguel P. Genetic analysis of ADIPOR1 and ADIPOR2 candidate polymorphisms for type 2 diabetes in the Caucasian population. Diabetes 2006; 55:856-61. [PMID: 16505255 DOI: 10.2337/diabetes.55.03.06.db05-0665] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Adiponectin is a metabolic link between adipose tissue and insulin action, mediating part of obesity-associated insulin resistance and type 2 diabetes. Two adiponectin receptors have been identified, and we investigated whether sequence variations in adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2) genes could contribute to the genetic risk for type 2 diabetes in a case-control study of 1,498 Caucasian subjects. We sequenced the putative functional regions of the two genes in 48 subjects and selected single nucleotide polymorphisms (SNPs) from the public database. Five SNPs in ADIPOR1 and 12 in ADIPOR2 were tested for association with type 2 diabetes. No SNP of ADIPOR1 showed association in any of the samples from the French population. In contrast, three SNPs of ADIPOR2 showed nominal evidence for association with type 2 diabetes before correction for multiple testing (odds ratio [OR] 1.29-1.37, P = 0.034-0.014); only rs767870, located in intron 6, was replicated in an additional diabetes dataset (n = 636, OR 1.29, P = 0.020) with significant allelic association from the overall meta-analysis of 2,876 subjects (adjusted OR 1.25 [95% CI 1.07-1.45], P = 0.0051). In conclusion, our data suggest a modest contribution of ADIPOR2 variants in diabetes risk in the French population.
Collapse
Affiliation(s)
- Martine Vaxillaire
- CNRS 8090, Institut de Biologie, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille, France.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Bouatia-Naji N, Meyre D, Lobbens S, Séron K, Fumeron F, Balkau B, Heude B, Jouret B, Scherer PE, Dina C, Weill J, Froguel P. ACDC/adiponectin polymorphisms are associated with severe childhood and adult obesity. Diabetes 2006; 55:545-50. [PMID: 16443793 DOI: 10.2337/diabetes.55.02.06.db05-0971] [Citation(s) in RCA: 123] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Common single nucleotide polymorphisms (SNPs) in the ACDC adiponectin encoding gene have been associated with insulin resistance and type 2 diabetes in several populations. Here, we investigate the role of SNPs -11,377C > G, -11,391G > A, +45T > G, and +276G > T in 2,579 French Caucasians (1,229 morbidly obese and 1,350 control subjects). We found an association between severe forms of obesity and -11,377C (odds ratio 1.23, P = 0.001) and +276T (1.19, P = 0.006). Surprisingly, alternative alleles -11,377G and +276G have been previously reported as risk factors for type 2 diabetes. Transmission disequilibrium tests showed a trend in overtransmission (56.7%) of a risk haplotype 1((C))-1((G))-1((T))-2((T)) including -11,377C and +276T in 634 obesity trios (P = 0.097). Family-based analysis in 400 trios from the general population indicated association between obesity haplotype and higher adiponectin levels, suggesting a role of hyperadiponectinemia in weight gain. However, experiments studying the putative roles of SNPs -11,377C > G and +276G > T on ACDC functionality were not conclusive. In contrast, promoter SNP -11,391G > A was associated with higher adiponectin levels in obese children (P = 0.005) and in children from the general population (0.00007). In vitro transcriptional assays showed that -11,391A may increase ACDC activity. In summary, our study suggests that variations at the ACDC/adiponectin gene are associated with risk of severe forms of obesity. However, the mechanisms underlying these possible associations are not fully understood.
Collapse
Affiliation(s)
- Nabila Bouatia-Naji
- Centre National de la Recherche Scientifique UMR8090, Pasteur Institute of Lille, France
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
49
|
Tankó LB, Siddiq A, Lecoeur C, Larsen PJ, Christiansen C, Walley A, Froguel P. ACDC/adiponectin and PPAR-gamma gene polymorphisms: implications for features of obesity. OBESITY RESEARCH 2005; 13:2113-21. [PMID: 16421345 DOI: 10.1038/oby.2005.262] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVE The main purpose of this study was to investigate associations of single-nucleotide polymorphisms (SNPs) in the adipocyte C1q and collagen domain-containing (ACDC) gene and its regulator, the nuclear peroxisome proliferator-activated receptor (PPAR)-gamma gene, with body fat mass and its topographical distribution in postmenopausal women. RESEARCH METHODS AND PROCEDURES Participants were 1501 healthy women, 60 to 85 years old, who were genotyped for four SNPs in the ACDC gene (-11391G/A, -11377C/G, +45T/G, +276G/T) and the Pro12Ala SNP in the PPAR-gamma gene. Total body fat mass and the central to peripheral fat mass ratio (CFM/PFM ratio) were measured using DXA. Adiponectin and homeostasis model assessment of insulin resistance were measured in 287 subjects. RESULTS The -11377C/G SNP was associated with adiponectin (p < 0.001) and the CFM/PFM ratio (p = 0.005); the G allele being associated with low adiponectin and high CFM/PFM ratio. Similar associations of adiponectin (p = 0.0001) and the CFM/PFM ratio (p = 0.002) characterized the 1_2 (G_G) promoter haplotype (11391G/A_-11377C/G). Genotype variation of SNP Pro12Ala was associated with total body fat mass (p = 0.04); women with GG being the most obese (p = 0.01). The Ala/Ala (GG) genotype of Pro12Ala SNP interacted with the CC genotype of SNP-11377C/G in the determination of BMI (p = 0.001), when analyzed using a codominant model. DISCUSSION Polymorphisms in the ACDC gene are associated with body fat distribution, whereas the Pro12Ala polymorphism in PPAR-gamma is associated with overall adiposity, apparently in interaction with an ACDC promoter SNP.
Collapse
Affiliation(s)
- László B Tankó
- Center for Clinical and Basic Research, Ballerup, Denmark.
| | | | | | | | | | | | | |
Collapse
|
|
50
|
Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptin--the classical, resistin--the controversical, adiponectin--the promising, and more to come. Best Pract Res Clin Endocrinol Metab 2005; 19:525-46. [PMID: 16311215 DOI: 10.1016/j.beem.2005.07.008] [Citation(s) in RCA: 308] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
With the growing prevalence of obesity, scientific interest in the biology of adipose tissue has been extended to the secretory products of adipocytes, since they are increasingly shown to affect several aspects in the pathogenesis of obesity-related diseases. The cloning of the ob gene is consistent with this concept and suggests that body fat content in adult rodents is regulated by a negative feedback loop centred in the hypothalamus. In recent years, a number of additional signalling molecules secreted by adipose tissue have been discovered, commonly referred to as 'adipocytokines'. Among these, adiponectin is perhaps the most interesting and promising compound for the clinician since it has profound protective actions in the pathogenesis of diabetes and cardiovascular disease. Adiponectin is low in obese subjects and, in particular, insulin-resistant patients. In contrast, resistin seems to be of greater relevance in relation to the immune stress response than in the regulation of glucose homeostasis. However, inflammatory processes have recently been connected with the development of atherosclerosis. Finally, little is known regarding the clinical relevance of visfatin. Recent research has revealed many functions of adipocytokines extending far beyond metabolism, such as immunity, cancer and bone formation. This report aims to review some of the recent topics of adipocytokine research that may be of particular importance.
Collapse
Affiliation(s)
- Antje Koerner
- University Hospital for Children and Adolescents, University of Leipzig, Oststrasse 21-25, Germany.
| | | | | |
Collapse
|