regulation of insulin and leptin signaling by muscle suppressor of cytokine signaling 3 (socs3)调节胰岛素和瘦素信号由肌肉抑制细胞因子信号3(socs3).pdfVIP

Regulation of Insulin and Leptin Signaling by Muscle Suppressor of Cytokine Signaling 3 (SOCS3) 1,2 3 3 4 4 5 Zhenggang Yang , Matthew Hulver , Ryan P. McMillan , Lingzhi Cai , Erin E. Kershaw , Liqing Yu , Bingzhong Xue1,6*, Hang Shi1,6* 1 Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America, 2 State Key Laboratory of Infectious Disease Diagnosis and Treatment, First Affiliated Hospital of Zhejiang University, Hang Zhou, China, 3 Department of Human Nutrition, Foods, and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America, 4 Division of Endocrinology, Diabetes, and Metabolism, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 5 Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, United States of America, 6 Department of Biology, Georgia State University, Atlanta, Georgia, United States of America Abstract Skeletal muscle resistance to the key metabolic hormones, leptin and insulin, is an early defect in obesity. Suppressor of cytokine signaling 3 (SOCS3) is a major negative regulator of both leptin and insulin signaling, thereby implicating SOCS3 in the pathogenesis of obesity and associated metabolic abnormalities. Here, we demonstrate that SOCS3 mRNA expression is increased in murine skeletal muscle in the setting of diet-induced and genetic obesity, inflammation, and hyperlipidemia. To further evaluate the contribution of muscle SOCS3 to leptin and insulin resistance in obesity, we generated transgenic mice with muscle-specific overexpression of SOCS3 (MCK/SOCS3 mice). Despite similar body weight, MCK/SOCS3 mice develop