Myostatin: Expanding horizons

Abstract

Myostatin is a secreted growth and differentiation factor that belongs to the TGF-β superfamily. Myostatin is predominantly synthesized and expressed in skeletal muscle and thus exerts a huge impact on muscle growth and function. In keeping with its negative role in myogenesis, myostatin expression is tightly regulated at several levels including epigenetic, transcriptional, post-transcriptional, and post-translational. New revelations regarding myostatin regulation also offer mechanisms that could be exploited for developing myostatin antagonists. Increasingly, it is becoming clearer that besides its conventional role in muscle, myostatin plays a critical role in metabolism. Hence, molecular mechanisms by which myostatin regulates several key metabolic processes need to be further explored.

Genetic Control of Lyme Arthritis by Borrelia burgdorferi Arthritis–Associated Locus 1 Is Dependent on Localized Differential Production of IFN-β and Requires Upregulation of Myostatin

“…6, 7, Table I). This was surprising given that myostatin is widely appreciated for its role as a negative regulator of skeletal muscle growth and regeneration (68), and intensely investigated for its positive impact on food production in the animal agriculture industry. Nevertheless, we were able to utilize a newly developed reagent in the field of muscle development to inhibit myostatin protein activity in vivo and discovered that myostatin is a direct mediator of Bbaa1 Lyme arthritis development (Fig.…”

“…Myostatin directed therapies are an appealing distinction from classic anti-inflammatory targets, as anti-bacterial responses are expected to remain intact. Additionally, myostatin inhibition is currently in various stages of clinical trials for patients with muscle wasting conditions and receiving attention as a potential therapeutic target for many metabolic disorders (68), studies which could provide insight into potential for inflammatory disorders such as arthritis as well.…”

Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives

“…[16][17][18] Moreover, skeletal muscle and beige fat are functionally linked, as physical activity releases myokines which increase beige fat and insulin signalling. [19][20][21][22] While the muscle responds directly to insulin by translocation of GLUT4 to the sarcoplasmic membrane, myokines likewise influence whole-body metabolism of glucose and lipids, as they have been repeatedly shown to act on adipose, liver, pancreas and intestine tissues. [16][17][18] The rising prevalence of insulin resistance in the general population highlights the need for a better understanding of its pathogenesis.…”

“…[16][17][18] Increasing skeletal muscle mass and activity are ways to increase energy expenditure and decrease adiposity with associated improvements in insulin resistance. [19][20][21][22][23][24] As described in more detail below, over 100 myokines have been identified by proteomics approaches and more than 250 putative myokines were reported based on GWAS and transcriptomics analyses. Skeletal muscle is one of the main targets of insulin because it is responsible for more than 60% of insulinstimulated clearance of glucose from the circulation; of note, muscle is one of the first tissues to develop insulin resistance and importantly, insulin action is greatly influenced by physical activity.…”

Comparative Skeletal Muscle Proteomics Using Two-Dimensional Gel Electrophoresis

“…The developing rat tibialis anterior [158] and porcine longissimus dorsi muscle [159] showed a time-dependent increase in contractile proteins and drastic alterations in metabolic enzymes, cytoskeletal proteins, molecular chaperones and signal transduction factors. An interesting negative regulator of muscle growth is myostatin, a secreted differentiation factor that belongs to the TGF-β superfamily [163]. Semitendious muscles from Belgium Blue bulls that lack myostatin were shown to be characterized by a higher proportion of fast-twitch glycolytic fibers with alterations in contractile protein isoform expression patterns and an increase in myosin binding protein MBP-H [164,165].…”