Coordinated maintenance of muscle cell size control by AMP-activated protein kinase.

Skeletal muscle mass is regulated by signaling pathways that govern protein synthesis and cell proliferation, and the mammalian target of rapamycin (mTOR) plays a key role in these processes. Recent studies suggested the crucial role of AMP-activated protein kinase (AMPK) in the inhibition of protein synthesis and cell growth. Here, we address the role of AMPK in the regulation of muscle cell size in vitro and in vivo. The size of AMPK-deficient myotubes was 1.5-fold higher than for controls. A marked increase in p70S6K Thr389 and rpS6 Ser-235/236 phosphorylation was observed concomitantly with an up-regulation of protein synthesis rate. Treatment with rapamycin prevented p70S6K phosphorylation and rescued cell size control in AMPK-deficient cells. Importantly, myotubes lacking AMPK were resistant to further cell size increase beyond AMPK deletion alone, as MyrAkt-induced hypertrophy was absent in these cells. Moreover, in skeletal muscle-specific deficient AMPKα1/α2 KO mice, soleus muscle showed a higher...