The central role of myostatin in skeletal muscle and whole body homeostasis.

Myostatin is a powerful negative regulator of skeletal muscle mass in mammalian species. It plays a key role in skeletal muscle homeostasis and has now been well described since its discovery. Myostatin is capable of inducing muscle atrophy via its inhibition of myoblast proliferation, increasing ubiquitin-proteasomal activity and downregulating activity of the IGF-Akt pathway. These well-recognized effects are seen in multiple atrophy causing situations, including injury, diseases such as cachexia, disuse and space flight, demonstrating the importance of the myostatin signalling mechanism. Based on this central role, significant work has been pursued to inhibit myostatin's actions in vivo. Importantly, several new studies have uncovered roles for myostatin distinct from skeletal muscle size. Myostatin has been suggested to play a role in cardiomyocyte homeostasis, glucose metabolism and adipocyte proliferation, all of which are examined in detail below. Based on these effects, myostatin inhibition has potential to be widely utilized in many Western diseases such as chronic obstructive pulmonary disease, type II diabetes and obesity. However, if myostatin inhibitors are to successfully translate from bench-top to bedside in the near future, awareness must be raised on these non-traditional effects of myostatin away from skeletal muscle. Indeed, further research into these novel areas is required.