Myostatin Attenuation In Vivo Reduces Adiposity, but Activates Adipogenesis

Abstract

A potentially novel approach for treating obesity includes attenuating myostatin as this increases muscle mass and decreases fat mass. Notwithstanding, conflicting studies report that myostatin stimulates or inhibits adipogenesis and it is unknown whether reduced adiposity with myostatin attenuation results from changes in fat deposition or adipogenesis. We therefore quantified changes in the stem, transit amplifying and progenitor cell pool in white adipose tissue (WAT) and brown adipose tissue (BAT) using label-retaining wild-type and mstn(-/-) (Jekyll) mice. Muscle mass was larger in Jekyll mice, WAT and BAT mass was smaller and label induction was equal in all tissues from both wild-type and Jekyll mice. The number of label-retaining cells, however, dissipated quicker in WAT and BAT of Jekyll mice and was only 25% and 17%, respectively, of wild-type cell counts 1 month after induction. Adipose cell density was significantly higher in Jekyll mice and increased over time concomitant with label-retaining cell disappearance, which is consistent with enhanced expansion and differentiation of the stem, transit amplifying and progenitor pool. Stromal vascular cells from Jekyll WAT and BAT differentiated into mature adipocytes at a faster rate than wild-type cells and although Jekyll WAT cells also proliferated quicker in vitro, those from BAT did not. Differentiation marker expression in vitro, however, suggests that mstn(-/-) BAT preadipocytes are far more sensitive to the suppressive effects of myostatin. These results suggest that myostatin attenuation stimulates adipogenesis in vivo and that the reduced adiposity in mstn(-/-) animals results from nutrient partitioning away from fat and in support of muscle.

CRISPR/Cas9‐mediated sheep MSTN gene knockout and promote sSMSCs differentiation

“…It inhibits the activity and expression of cyclin‐dependent kinase family through positive regulation of p21 to maintain the satellite cell resting state. In contrast, MSTN gene can promote the phosphorylation of SMAD3 to inhibit the expression of MyoD gene, so that myoblasts could not differentiate into myotubes …”

Polymorphism of Myostatin (MSTN) Promoter Gene and its Association with Growth and Muscling Traits in Bali Cattle

“…However, MSTN expression did not disturbed other myogenic expressions, such as Myog, Myf5, and MyoD and increased muscle mass. Futhermore, this mutation was able to reduce adiposity both of white fat and brown fat affected by neighboring muscle fiber (Li et al, 2015). Myostatin significantly inhibited differentiation of preadipocyte by cytokine from muscle fiber (Li et al, 2015).…”

“…Futhermore, this mutation was able to reduce adiposity both of white fat and brown fat affected by neighboring muscle fiber (Li et al, 2015). Myostatin significantly inhibited differentiation of preadipocyte by cytokine from muscle fiber (Li et al, 2015). Moreover, they play cross role in muscle-fat which might regulate fat ratio in muscle such as IMF percentage (Sun et al, 2016).…”

Myostatin serum concentrations are correlated with the severity of knee osteoarthritis

“…5 Myostatin negatively regulates skeletal muscle growth. It is mainly expressed in skeletal muscles but is also found in cardiac muscles, blood, and adipose tissues.…”

“…It is mainly expressed in skeletal muscles but is also found in cardiac muscles, blood, and adipose tissues. 5 Myostatin negatively regulates skeletal muscle growth. 6 Inactivation of the myostatin gene expression in mice accelerates muscle growth.…”