title: Metformin and resveratrol ameliorate muscle insulin resistance through preventing lipolysis and inflammation in hypoxic adipose tissue.
abstract: This study aims to investigate the effects of metformin and resveratrol on muscle insulin resistance with emphasis on the regulation of lipolysis in hypoxic adipose tissue. ICR mice were fed with high fat diet (HFD) for 10days with administration of metformin, resveratrol, or intraperitoneal injection of digoxin. Adipose hypoxia, inflammation and cAMP/PKA-dependent lipolysis were investigated. Moreover, lipid deposition and insulin resistance were examined in the muscle. Metformin and resveratrol attenuated adipose hypoxia, inhibited HIF-1α expression and inflammation in the adipose tissue of HFD-fed mice. Metformin and resveratrol inhibited lipolysis through prevention of PKA/HSL activation by decreasing the accumulation of cAMP via preserving PDE3B. Metformin and resveratrol reduced FFAs influx and DAG accumulation, and thus improved insulin signaling in the muscle by inhibiting PKCθ translocation. This study presents a new view of regulating lipid metabolism to ameliorate insulin resistance and provides the clinical guiding significance for obesity and type 2 diabetes with metformin and resveratrol treatment.
authors.affiliation: Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicines, Nanjing 211198, China.
authors.forename: Aiyun
authors.initials: A
authors.lastname: Li
authors.affiliation: Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Feng
authors.affiliation: Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicines, Nanjing 211198, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicines, Nanjing 211198, China.
authors.forename: Baolin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: ningzh18@yeah.net.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000473:pathology*; D000284:Administration, Oral; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D059305:Diet, High-Fat; D004075:Diglycerides / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005247:Feeding Behavior; D005947:Glucose / Q000378:metabolism; D000860:Hypoxia / Q000150:complications / Q000473:pathology*; D007249:Inflammation / Q000150:complications / Q000473:pathology* / Q000517:prevention & control; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D009132:Muscles / Q000473:pathology*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004075:Diglycerides; D005227:Fatty Acids; D007328:Insulin; D013267:Stilbenes; D008687:Metformin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; D000077185:Resveratrol
keywords: Hypoxia; Insulin resistance; Lipolysis; Metformin; Resveratrol