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adiponectin alleviates contractile dysfunction of genioglossus in rats exposed to chronic intermittent hypoxia

Chinese Medical Journal 2013年第17期126卷 3259-3263页

作者： WANG Wen-jing LU Gan DING Ning, HUANG Han-peng DING Wen-xiao ZHANG Xi-long Department of Respiratory Medicine Nanjing Hospital Affiliated to Nanjing Medical University Nanjing Jiangsu 210001 China Department of Respiratory Medicine Jiangsu Geriatric Hospital Nanjing Jiangsu 210024 China Department of Respiratory Medicine First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu 210029 China

Background Genioglossal dysfuntion takes an important role in pathogenesis of obstructive sleep apnea hypopnea syndrome （OSAHS） in which chronic intermittent hypoxia （CIH） is the major pathological origin. Recent studies have suggested genioglossal injury induced by CIH might be improved by adiponectin. The aim of this study was to investigate the effects of adiponectin on genioglossus contractile properties in rats exposed to CIH. Methods Thirty-nine healthy male Wistar rats were randomly divided into three groups： normal control （NC）, CIH and adiponectin supplement （CIH＋Ad） with 13 rats in each. Rats in NC were kept breathing normal air, while rats in CIH and CIH＋Ad experienced the same CIH environment eight hours per day for 35 successive days. Rats in CIH＋Ad were given intravenous adiponectin of 10 IJg twice a week for 30 successive days. Rats in the NC and CIH were injected with normal saline as a control. After 35 days＇ CIH exposure, the levels of serum adiponectin and genioglossus contractile properties were compared. Results Serum adiponectin level was significantly lower in CIH than in NC （1210 ng/ml vs. 2236 ng/ml）. Serum adiponectin level in CIH＋Ad （1844 ng/ml） was significantly higher than CIH but lower than NC. Twitch tension, time to peak tension, half relaxation time and tetanic tension were significantly lower in CIH than NC and improved in CIH＋Ad. All mean tetanic fatigue indices decreased more rapidly in the first 20 seconds than during the subsequent 100 seconds. Tetanic fatigue indices in NC and CIH＋Ad were significantly higher compared to CIH. Conclusions CIH could lead to hypoadiponectinaemia, impaired genioglossus contractile properties and decreased fatigue resistance in rats. Such changes could be partially offset by supplementation of adiponectin.

关键词： obstructive sleep apnea hypopnea syndrome adiponectin intermittent hypoxia genioglossus

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adiponectin gene polymorphisms and risk of gestational diabetes mellitus:A meta-analysis

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World Journal of Clinical Cases 2019年第5期7卷 572-584页

作者： Lin-Ting Huang Shi-Lan Wu Xin Liao Shu-Juan Ma Hong-Zhuan Tan Department of Epidemiology and Health Statistics Xiangya School of Public Health Central South University

BACKGROUND adiponectin(ADIPOQ) is an important factor involved in the regulation of both carbohydrate and lipid metabolism. Polymorphisms in the ADIPOQ gene are known to influence an individual's predisposition to metabolic syndrome and type 2 diabetes. Moreover, women with gestational diabetes mellitus(GDM) are at an increased risk of developing type 2 diabetes. Several studies have been conducted previously to assess the association between ADIPOQ polymorphisms and GDM; however, the results of the association are inconclusive.AIM To quantitatively evaluate the association between ADIPOQ +45 T/G, +276 G/T,and-11377 C/G polymorphisms and the risk of GDM.METHODS A systematic search of EMBASE, PubMed, CNKI, Web of Science, and WANFANG DATA was conducted up to October 20, 2018. We calculated merged odds ratios(ORs) with 95% confidence intervals(CIs) using a fixed-effects or random-effects model depending on the between-study heterogeneity to evaluate the association between AIDPOQ +45 T/G, +276 G/T, and-11377 C/G polymorphisms and the risk of GDM. Subgroup analysis was performed by ethnicity. Publication and sensitivity bias analyses were performed to test the robustness of the association. All statistical analyses were conducted using Stata 12.0.RESULTS Nine studies of +45 T/G included 1024 GDM cases and 1059 controls, five studies of +276 G/T included 590 GDM cases and 595 controls, and five studies of-11377 C/G included 722 GDM cases and 791 controls. Pooled ORs indicated that+45 T/G increased GDM risk in Asians(allelic model: OR = 1.47, 95%CI: 1.27-1.70,P = 0.000; dominant model: OR = 1.54, 95%CI: 1.27-1.85, P = 0.000; recessive model: OR=2.00, 95%CI: 1.43-2.85, P = 0.000), not in South Americans(allelic model: OR = 1.21, 95%CI: 0.68-2.41, P = 0.510; dominant model: OR = 1.13, 95%CI:,0.59-2.15, P = 0.710; recessive model: OR = 2.18, 95%CI: 0.43-11.07, P = 0.350).There were no significant associations between +276 G/T(allelic model: OR = 0.88,95%CI: 0.74-1.05, P = 0.158; dominant model: OR = 0.91, 95%CI: 0.65-1.2

关键词： Gestational diabetes mellitus Single nucleotide Polymorphism adiponectin Gene Meta-analysis

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adiponectin affects the mechanical responses in strips from the mouse gastric fundus

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World Journal of Gastroenterology 2018年第35期24卷 4028-4035页

作者： Eglantina Idrizaj Rachele Garella Giovanni Castellini Hermine Mohr Natalia S Pellegata Fabio Francini Valdo Ricca Roberta Squecco Maria Caterina Baccari Department of Experimental and Clinical Medicine Section of Physiological Sciences University of Florence Psychiatry Unit Department of Health Sciences University of Florence Institute for Diabetes and Cancer Helmholtz Zentrum München

AIM To investigate whether the adipocytes derived hormone adiponectin(ADPN) affects the mechanical responses in strips from the mouse gastric fundus. METHODS For functional experiments, gastric strips from the fundal region were cut in the direction of the longitudinal muscle layer and placed in organ baths containing KrebsHenseleit solution. Mechanical responses were recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation(EFS) was applied via two platinum wire rings through which the preparation was threaded. The effects of ADPN were investigated on the neurally-induced contractile and relaxant responses elicited by EFS. The expression of ADPN receptors, Adipo-R1 and Adipo-R2, was also evaluated by touchdown-PCR analysis. RESULTS In the functional experiments, EFS(4-16 Hz) elicited tetrodotoxin(TTX)-sensitive contractile responses. Addition of ADPN to the bath medium caused a reduction in amplitude of the neurally-induced contractile responses(P 0.05). The direct smooth muscle response to methacholine was not influenced by ADPN(P > 0.05). In carbachol precontracted strips and in the presence of guanethidine, EFS induced relaxant responses. Addition of ADPN to the bath medium, other than causing a slight and progressive decay of the basal tension, increased the amplitude of the neurally-induced relaxant responses(P < 0.05). Touchdown-PCR analysis revealed the expression of both Adipo-R1 and Adipo-R2 in the gastric fundus.CONCLUSION The results indicate for the first time that ADPN is able to influence the mechanical responses in strips from the mouse gastric fundus.

关键词： adiponectin adiponectin receptors Gastric motility Nitric oxide Non-adrenergic,non-cholinergic neurotransmission

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adiponectin receptor 1 mediates the difference in adiponectininduced prostaglandin E2 production in rheumatoid arthritis and osteoarthritis synovial fibroblasts

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Chinese Medical Journal 2011年第23期124卷 3919-3924页

作者： ZUO Wei WU Zhi-hong WU Nan DUAN Yuan-hui WU Ju-tai WANG Hai QIU Gui-xing Department of Orthopedics Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 China

The synovial fluid concentrations of adiponectin are significantly higher in patients with rheumatoid arthritis （RA） than in patients with osteoarthritis （OA）. Accumulating evidence suggests that adiponectin may be an inducer of inflammation in arthritis, but the mechanism remains unclear. The objectives of this study were to compare the expression levels of adiponectin receptors in rheumatoid arthritis synovial fibroblasts （RASF） and osteoarthritis synovial fibroblasts （OASF）, evaluate the roles of adiponectin receptors in adiponectin-induced prostaglandin E2 （PGE2） production, and then investigate the effects of a nonsteroidal anti-inflammatory drug （NSAID） and a cyclooxygenase （COX）-2-selective inhibitor on adiponectin-induced PGE2 release. Methods The expressions of adiponectin receptor 1 （AdipoR1） and AdipoR2 mRNA and protein in synovial fibroblasts from seven patients with RA and eight patients with OA undergoing total knee replacement were evaluated by real-time polymerase chain reaction, immunofluorescence microscopy and Western blotting analysis. adiponectin-induced PGE2 production was detected by enzyme-linked immunosorbent assay. RNA interference against the AdipoR1 and AdipoR2 genes was performed to investigate the effects of the adiponectin receptors on adiponectin-induced PGE2 production in both RASF and OASE Results AdipoR1 and AdipoR2 mRNA and protein were expressed by both RASF and OASF. Compared with OASF, RASF exhibited higher levels of AdipoR1, but there was no significant difference for AdipoR2. adiponectin induced the production of PGE2 by the synovial fibroblasts in a concentration-dependent manner, and this was more obvious in RASF. RNA interference showed that the difference may be mediated by the diverse distribution of AdipoRl. The adiponectin-induced PGE2 production was efficiently relieved by the NSAID and COX-2-selective inhibitor. Conclusion The present findings suggest that AdipoR1 may mediate the difference in adiponectin-induced PGE2 production in RASF and OASE

关键词： adiponectin rheumatoid arthritis osteoarthritis prostaglandin E2 fibroblast

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adiponectin serum level in chronic hepatitis C infection and therapeutic profile

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World Journal of Hepatology 2015年第1期7卷 44-52页

作者： Valentina Peta Carlo Torti Natasa Milic Alfredo Foca Ludovico Abenavoli Department of Health Sciences University Magna GraciaCampus Germaneto88100 CatanzaroItaly Department of Medical and Surgical Sciences University Magna GraeciaCampus Germaneto88100 CatanzaroItaly Department of Pharmacy University of Novi Sad21000 Novi SadSerbia

Hepatic steatosis is commonly seen in the patients with chronic hepatitis C virus(HCV) infection. HCV is closely associated with lipid metabolism,and viral steatosis is more common in genotype 3 infection owing to a direct cytopathic effect of HCV core protein. In non-genotype3 infection,hepatic steatosis is considered largely to be the result of the alterations in host metabolism; metabolic steatosis is primarily linked with HCV genotype 1. A d i p o s e t i s s u e s e c r e t e s d i f f e r e n t h o r m o n e s involved in glucose and lipid metabolisms. It has been demonstrated that adipocytokines are involved in the pathogenesis of non-alcoholic fatty liver disease,as the decreased plasma adiponectin levels,a soluble matrix protein expressed by adipoctyes and hepatocyte,are associated with liver steatosis. Various studies have shown that steatosis is strongly correlated negatively with adiponectin in the patients with HCV infection. The role of adiponectin in hepatitis C virus induced steatosis is still not completely understood,but the relationship between adiponectin low levels and liver steatosis is probably due to the ability of adiponectin to protect hepatocytes from triglyceride accumulation by increasing β-oxidation of free fatty acid and thus decreasing de novo free fatty acid production.

关键词： Hepatitis C virus adiponectin Metabolism Insulin resistance Hepatitis C virus core protein

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Comparison of Serum adiponectin in Smoke-induced Pulmonary Emphysema Rats Fed Different Diets

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Chinese Medical Journal 2016年第2期129卷 187-193页

作者： Rui-Ying Wang Hu Liu Li-JuanMa Jian-Ying Xu Department of Respiratory Diseases Shanxi Dayi Hospital Affiliated to Shanxi Medical University Taiyuan Shanxi 030032 China Department of Respiratory Diseases People's Hospital of Salt Lake Valley Yuncheng Shanxi 044000 China

Background： Smoking and body mass index （BMI） are the key risk factors for chronic obstructive pulmonary disease （COPD）. adiponectin with both anti-inflammatory and pro-inflammatory properties is a vital modulator of inflammatory processes, which is expressed in epithelial cells in the airway in COPD-emphysema. The aim of this study was to examine the effects of adiponectin on tobacco smoke-induced emphysema in rats, which were fed different diets. Methods： Seventy-six adult （6-8 weeks old） male Sprague-Dawley rats （average weight 220 ± 20 g） were exposed to smoke or smoke-free room atmosphere and fed different diets （regular, high-fat, or low-fat diets） for 6 months. The rats were randomly divided into six groups. They are nonsmoke-exposed regular diet （n = 10）, nonsmoke-exposed high-fat diet （n - 14）, nonsmoke-exposed low-fat diet （n = 14）, smoke-exposed regular diet （n = 10）, smoke-exposed high-fat diet （n = 14）, and smoke-exposed low-fat diet groups （n = 14）. A full 23 factorial design was used to evaluate the effect of independent variables on smoke exposure and different rearing methods. Serum adiponectin and inflammatory cytokines were measured by the enzyme-linked immunosorbent assay （ELISA）. Results： Serum adiponectin levels in rats fed low-fat and regular diets exposed to smoke exposure were remarkably higher than that of rats exposed to room air while serum adiponectin levels of fat-rich diet rats exposed to tobacco smoke were lower than that of rats exposed to room air. Compared with regular diet or low-fat diet group, serum adiponectin levels in high-fat diet rats exposed to tobacco smoke were lower （t = 6.932, 11.026; all P 〈 0.001 ）. BMI was inversely correlated with serum adiponectin levels （r = -0.751, P = 0.012）. Serum interleukin 6 （IL-6）, tumor necrosis factor-or （TNF-a）, and 4-hydroxy 2-nonenal （HNE） levels in rats exposed to low-fat or fat-rich diets were remarkably higher than that of rats exposed to normal diets （IL-6, t = 4.196, 3.480; P 〈 0.01, P = 0.001 ; TNF-a, t = 4.286, 3.521 ; P 〈 0

关键词： adiponectin Diet Pulmonary Emphysema Smoke

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Association between adiponectin and Metabolic Syndrome in Older Adults from Major Cities of China

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Biomedical and Environmental Sciences 2010年第1期23卷 53-61页

作者： QIN ZHUO ZHI-QING WANG PING FU JIAN-HUA PIAO YUAN TIAN JIE XU XIAO-GUANG YANG National Institute of Nutrition and Food Safety Chinese Center for Disease Control and Prevention Beijing 100050 China Centre for Chrom'c Diseases School of Medicine University of Queensland Brisbane QLD 4072 Australia

Objective To investigate the association between adiponectin and metabolic syndrome （MetS） and related diseases in older adults from major cities of China. Methods A total of 2 049 adults at the age of 60-96 years from18 major cities of China were enrolled in the study. Plasma adiponectin and insulin concentrations were measured. Insulin resistance was assessed by homeostasis model assessment of insulin resistance （HOMA-IR）. The definitions proposed by International Diabetes Federation （IDF） and American Heart Association/National Heart, Lung, and Blood/nstitute （AHA/NLHBI） were used to identify MetS. Results The adiponectin concentration increased with the advance of age and was higher in women than in men. The sex specific adiponectin concentration was inversely correlated with body mass index （BMI）, waist circumference, diastolic blood pressure, triglycerides, glucose and fasting blood insulin, and positively correlated with HDL-C （P〈0.001）. The adiponectin concentration decreased with increasing MetS components. Compared with the 4th sex-specific adiponectin quartile, the odds ratio （OR） for prevalent MetS-IDF and MetS-AHA/NLHBI in subjects of the 1st quartile group was 3.25 （95% CI： 2.24, 4.71） and 3.21 （95% CI： 2.26, 4.55）, respectively. The association was independent of age, sex, life-style factors, medication, family history of chronic diseases, BMI, and HOMA-IR, The OR for MetS was much higher than those of MetS components and its related diseases. Conclusion adiponectin is strongly associated with MetS independent of insulin resistance and obesity in older adults from major cities in China. The adiponectin concentration is a useful predictor for the risk of MetS.

关键词： adiponectin Metabolic syndrome Chinese older adults Obesity Insulin resistance

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The FGF21-adiponectin axis in controlling energy and vascular homeostasis

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分子细胞生物学报:英文版 2016年第2期8卷 110-119页

作者： Xiaoyan Hui Tianshi Feng Qing Liu Yuan Gao Aimin Xu State Key Laboratory of Pharmaceutical Biotechnology The University of Hong KongHong KongChina Department of Medicine The University of Hong KongHong KongChina Department of Pharmacy and Pharmacology The University of Hong KongHong KongChina

Whole-body energy metabolism and cardiovascular homeostasis are tightly controlled processes that involve highly coordinated crosstalk among distal organs.This is mainly achieved by a large number of hormones released from each organ.Among them,fibroblast growth factor 21(FGF21)and adiponectin have recently gained considerable attention,since both of them possess multiple profound protective effects against a myriad of cardio-metabolic disorders.Despite their distinct structuresand production sites,these two hormones share striking functional similarity.This dichotomy is recently reconciled by the demonstration of the FGF21-adiponectin axis.In adipocytes,both transcription and secretion of adiponectin are strongly induced by FGF21,which is partially dependent on PPARg activity.Furthermore,the glucose-lowering,lipid-clearing,and anti-atherosclerotic functions of FGF21 are diminished in adiponectin-null mice,suggesting that adiponectin serves as an obligatory mediator of FGF21-elicited metabolic and vascular benefits.However,in both animals and human subjects with obesity,circulating FGF21 levels are increased whereas plasma adiponectin concentrations are reduced,perhaps due to FGF21 resistance,suggesting that dysfunctional FGF21-adiponectin axis is an important contributor to the pathogenesis of obesity-related cardio-metabolic syndrome.The FGF21-adiponectin axis protects against a cluster of cardio-metabolic disorders via mediating multi-organ communications,and is a promising target for therapeutic interventions of these chronic diseases.

关键词： FGF21 adiponectin energy metabolism vascular homeostasis PPARγ

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Identification of a Regulatory Single Nucleotide Polymorphism in the adiponectin (APM1) Gene Associated with Type 2 Diabetes in Han Nationality

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Biomedical and Environmental Sciences 2008年第6期21卷 454-459页

作者： MIN YANG CHANG-CHUN QIU WEI CHEN LING-LING XU MIAO YU HONG-DING XIANG Department of Endocrinolog） Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing 100730 China National Laboratory of Medical Molecular Biology School of Basic Medicine Peking Union Medical College Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Beijing 100005 China

Objective To identify the genetic defects of the the adiponectin （APM1） gene that contribute to the development of type 2 diabetes （T2DM） and determine the functional single nucleotide polymorphisms （SNPs） in the APMI gene associated with T2DM in Han nationality. Methods The APMI gene 5＇-UTR was screened by direct sequencing to identify common polymorphisms. Identified SNPs were genotyped in 585 nondiabetic controls, 278 subjects with impaired glucose intolerance （IGT） and 212 patients with T2DM. The functions of SNPs in the regulatory region were assessed by reporter gene assay. Possible association between SNPs and plasma APMI levels or metabolic parameters was statistically asses,sed. Results Three SNPs were identified in the APMI gene 5＇-UTR. A case-control study revealed that SNP -11377 G/C had significant differences in allele frequencies between T2DM patients and nondiabetic controls （G 0.314/C 0.686 vs. G 0.265/C 0.735, P=0.03）. Haplotype analysis of three SNPs in the APM1 gene showed that no significant association of haplotypes with T2DM. IGT was detected in the present study. Reporter gene assay showed that SNP did not influence the transcription efficiency in the 3T3-LI cell line. Conclusion SNP - 11377 G/C in the proximal promoter region of the APM 1 gene contributes to the development of T2DM in Han nationality but may not be a functional SNP in the APM1 gene.

关键词： Diabetes adiponectin Single nucleotide polymorphism Reporter gene Promoter

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Association study of the single nucleotide polymorphisms in adiponectin-associated genes with type 2 diabetes in Han Chinese

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Journal of Genetics and Genomics 2009年第7期36卷 417-423页

作者： Yabing Wang Di Zhang Yun Liu Yifeng Yang Teng Zhao Jie Xu Sheng Li Zuofeng Zhang Guoyin Feng Lin He He Xu Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China Bio-X Center Shanghai Jiao Tong University Shanghai 200030 China Department ofEpidemiology UCLA School of Public Health Los Angeles California 90095-1772 USA Institutes of Biomedical Sciences Fudan University Shanghai 200032 China

Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs ofADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects, rs 16861194 （-11426 A〉G） in the putative promoter of ADIPOQ was associated with T2DM （P = 0.007; OR = 1.29, 95% CI 1.08-1.55）. None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs 16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.

关键词： adiponectin ADIPOQ ADIPORs SNP diabetes

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