Role of myostatin in metabolism

Abstract

Purpose of review: To review papers on myostatin published in 2003 and early 2004. Myostatin is a negative regulator of skeletal muscle mass produced in this tissue. Inactivating mutations of the myostatin gene or interaction of myostatin protein with follistatin and other inhibitory proteins induce a hypermuscular phenotype in cattle and mice; this is assumed to result from inhibition of muscle cell proliferation and DNA and protein synthesis (antianabolic effects). Myostatin also controls muscle mass in other animals, and appears to affect adipose tissue mass.

Recent findings: New protein interactions inhibiting myostatin that lead to double muscling, as well as the induction of hypermuscularity with myostatin antibodies, or the generation of a myostatin conditional knockout mouse, have been reported. Conversely, a transgenic mouse over-expressing myostatin and exhibiting reduced muscle mass in a gender-specific process has been obtained. In addition, novel inactivating mutations in the myostatin gene and genetic loci regulating myostatin effects, and the characterization of the myostatin gene and its effects on metabolism in fish and chicken have been described. Finally, the regulation of myostatin levels by growth hormone, glucorticoids, anabolic agents, nutritional status and exercise, the characterization of myostatin signaling pathways, and the clarification of myostatin effects on cell replication and differentiation, are other important recent findings.

Summary: These studies suggest that proteins and drugs that inactivate myostatin, or interfere with its binding to its receptor, may be useful for the therapy of wasting and degenerative muscle diseases and for the food industry. Other promising approaches may derive from new insights into the biochemical cascade that mediates myostatin effects, and into the role of myostatin in the regulation of fat metabolism and of heart and muscle regeneration after injury.