myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity肌肉生长抑制素抑制肌肉,而不是脂肪组织,脂肪量,改善胰岛素敏感性降低.pdfVIP

Myostatin Inhibition in Muscle, but Not Adipose Tissue, Decreases Fat Mass and Improves Insulin Sensitivity 1 2 2 1 2 Tingqing Guo , William Jou , Tatyana Chanturiya , Jennifer Portas , Oksana Gavrilova , Alexandra C. McPherron1* 1 Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Mouse Metabolic Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America Abstract Myostatin (Mstn) is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn2/ 2 mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet- induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn2/ 2 mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn2/ 2 mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn2/ 2 mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue