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

Abstract

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.

Sex-specific differences in risk factors for sarcopenia amongst community-dwelling older adults

“…There is thus greater impetus to examine the differential effects of IGF-1, potentially remediable through exercise and nutritional interventions (Yamada et al 2015). Myostatin has received recognition as a potent inhibitor of skeletal muscle growth (Elliot et al 2012), further supported by animal models evidencing muscle hypertrophy with myostatin gene deletion while its overexpression in transgenic mice was associated with lower muscle mass (Reisz-Porszasz et al 2003). Indeed, myostatin is already emerging as a promising therapeutic target for muscle health, with myostatin antibody demonstrating increase in muscle mass amongst persons with muscle dystrophy, and its pharmacological inhibition leading to improved lean mass in patients undergoing androgen deprivation therapy for prostate cancer (Wagner et al 2008;Padhi et al 2014).…”

An Antibody Blocking Activin Type II Receptors Induces Strong Skeletal Muscle Hypertrophy and Protects from Atrophy

“…This is because of the dramatic hypertrophy seen in a variety of myostatin-null animals and in a human who was null for this ligand (5)(6)(7)(8)(9). Some interesting correlations between myostatin levels and cachexic muscle loss have been reported in preclinical mouse models, as well as in human diseases (43). However, the levels of myostatin reported in humans are lower than those seen in rodents (44)(45)(46), and even in rodents, more modest effects are seen when myostatin is blocked in adult animals (33,47) than when it is blocked during development.…”

The effect of myostatin on proliferation and lipid accumulation in 3T3-L1 preadipocytes

“…from three independent experiments. *P!0.05 and It has been shown that myostatin is capable of inhibiting myoblast proliferation, which thereby induces muscle atrophy (Elliott et al 2012). Additionally, results from a number of studies have indicated that myostatin also inhibits the proliferation of a variety of cells, including NIH3T3 fibroblasts (Hosaka et al 2012), rhabdosphincter satellite cells (Akita et al 2013), and primary myosatellite cells from rainbow trout (Garikipati & Rodgers 2012).…”