Role of myokines in the maintenance of whole-body metabolic homeostasis.

Obesity is reaching epidemic proportions in developed countries and is on the rise in developing countries. Obesity-related changes in lipid and glucose metabolism predispose to the development of metabolic syndrome and type 2 diabetes. Skeletal muscle constitutes about 40 percent of total body weight and is unique compared to other muscle types since it is one of the most important organs for insulin-dependent glucose metabolism in humans. Abnormalities in skeletal muscle lipid and glucose metabolism as well as abnormal accumulation of intramyocellular lipids could predispose for the development of type 2 diabetes. Skeletal muscle synthesizes and secretes factors with autocrine/paracrine/endocrine functions that can regulate skeletal muscle metabolism as well as affect other organs. These factors secreted by skeletal muscle are called myokines. Secretion and action of myokines is regulated by physiological conditions. Some myokines have positive effect on metabolism, improving functions of multiple organs. Yet, other myokines are released under pathological conditions and might exacerbate abnormal metabolic functions. Expression and/or secretion of a number of myokines are regulated by exercise and therefore might mediate positive effects of physical activity on whole-body metabolism. In the current review we summarized current knowledge on some of the myokines with important physiological functions in lipid and glucose metabolism. A better understanding of the effects of myokines on whole-body metabolism can aid in development of the future pharmacologic therapies for counteracting the current worldwide obesity epidemic and obesity-mediated abnormalities.