Increasing Muscle Mass by Deletion of Myostatin Improves Metabolic and Vascular Function in Obese (db/db) Mice

Abstract

Obesity is the major emerging risk factor in the disease burden of western cultures. Obesity significantly reduces both metabolic and cardiovascular function, most notably inducing a state of insulin resistance in the former case and impeding endothelial control of vascular function in the latter. Mechanisms underpinning these defects are poorly understood and interventional therapies remain few. Exercise is a powerful method to limit or improve obesity-associated diseases, improving metabolic syndrome markers and endothelial function in obese patients. The salutatory effects of exercise are multi-factorial and include increases in muscle size and quality, reduction in fat mass and alterations in the components of plasma milieu. The relationships between the physiologic changes induced by exercise and improvements in metabolic and cardiovascular function are poorly defined. Myostatin, a TGF-β family member, is secreted by muscle, limits muscle growth and stimulates adipose tissue accumulation. Thus deletion of myostatin permits a method of assessing whether a component of exercise, increases in muscle mass, has positive effects on metabolic and vascular function. While myostatin deletion can improve glucose tolerance, the mechanisms are unclear. Whether myostatin deletion improves endothelial function in obesity is also not clear. The overall goal of the current study was to determine if increasing muscle mass by deletion of myostatin improves metabolic and vascular function in obese (db/db) mice.