Myostatin regulates glucose uptake in BeWo cells

Abstract

Myostatin is a member of the transforming growth factor (TGF)-β superfamily, known for its ability to inhibit muscle growth. It can also regulate metabolism and glucose uptake in a number of tissues. To determine the mechanism of myostatin's effect on glucose uptake, we evaluated its actions using choriocarcinoma cell lines that are widely used as models for placental cells. Protein and mRNA were determined using immunoblotting and RT-PCR/PCR, respectively. Glucose uptake was assessed by uptake of radiolabeled deoxyglucose in vitro. All choriocarcinoma cell lines tested i.e., BeWo, JEG, and Jar, are used as models of placental cells, and all expressed myostatin protein and mRNA. Treatment of BeWo cells with myostatin resulted in inhibition of glucose uptake in a concentration-dependent manner ( P < 0.01). At all concentrations tested, follistatin, a functional inhibitor of myostatin, completely blocked the inhibitory effect of myostatin (40 nM) on glucose uptake by BeWo cells (0.4 nM, P < 0.05). Follistatin treatment alone also increased glucose uptake (0.4 and 4 nM, P < 0.001; 40 nM, P < 0.05). Because BeWo cells proliferated and greater cell densities were achieved, glucose uptake declined irrespective of treatment. Myostatin treatment of BeWo cells did not alter the levels of myostatin receptor, ActRII A/B proteins. The levels of glucose transport proteins also remained unaltered in BeWo cells with myostatin treatment. This study has shown that myostatin specifically inhibits glucose uptake into BeWo cells, suggesting that locally produced myostatin may control glucose metabolism within the placenta.

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

“…The effect of myostatin on placental glucose transport is mixed, with decreased glucose transport in a choriocarcinoma cell line (27) and increased transport in human placental explants (28). Myostatin also promotes extravillous trophoblast migration in vitro, which may alter placental development in vivo (29).…”

Increased Secretion and Expression of Myostatin in Skeletal Muscle From Extremely Obese Women

“…Whether this is due solely to increased lean muscle mass or other metabolic effects of reduced circulating myostatin have yet to be determined (33). Recent studies, however, have shown that myostatin inhibits glucose uptake in placental cell lines, suggesting that it may contribute to systemic insulin resistance with obesity (35). Others have implicated myostatin in a network of genes potentially regulated by insulin with extreme obesity (30).…”

“…This may contribute to systemic metabolic deterioration of skeletal muscle with the progression of insulin resistance to type 2 diabetes. Diabetes 58: [30][31][32][33][34][35][36][37][38] 2009 O besity and type 2 diabetes are associated with endocrine abnormalities that are either precipitated by or precede the onset of peripheral insulin resistance (1). These include changes in circulating proteins and peptides that produce endothelial dysfunction, low-grade inflammation, and a prothrombotic state, all of which contribute to increased cardiovascular risk (2-4).…”

Placental expression of myostatin and follistatin-like-3 protein in a model of developmental programming

“…Mitchell et al (29) have shown that there is a negative correlation in human placenta between myostatin expression and gestational age, with a higher myostatin expression evident in preterm human placental tissues compared with term placental tissues. Additional in vitro studies also found that myostatin regulates glucose uptake in human placenta (3,29).…”