Myostatin inhibition improves insulin signaling in muscles of mice with high fat diet‐induced diabetes

Abstract

Myostatin inhibits skeletal muscle growth. Animals lacking myostatin develops significantly larger muscles, which are associated with reduced adiposity and lower blood glucose. We investigated whether myostatin inhibition would improve the metabolic profile of diabetic mice. C56/BL6 mice were fed a high fat diet (HFD) for 10 months. During the last 3 weeks, myostatin was inhibited by injections of a myostatin peptibody in mice on HFD vs PBS injected mice on a HFD. Body weight, lean mass and adipose tissue were quantified using an x‐ray imager; oxygen consumption and carbon dioxide production were measured using an animal monitoring system. Myostatin inhibition (MI) decreased blood glucose, serum insulin and increased glucose disposal in response to insulin. Also, there was increase in energy expenditure, associated with a decrease in the percent body fat plus a decrease in serum fatty acids. MI also increased p‐Akt in both muscle and white adipose tissue (WAT), responses linked to increased expression of fatty acid oxidation genes, plus an increase in AMPK activation plus expression of PPAR. We propose that myostatin, by suppressing both the AMPK and PPAR axes in skeletal muscle and adipose tissue interferes with insulin signaling and reduces fatty acid oxidation. In conclusion, targeting myostatin corrects these defects improving both insulin signaling and lipid metabolism in diabetes.