| First Author | Koo JH | Year | 2017 |
| Journal | J Clin Invest | Volume | 127 |
| Issue | 10 | Pages | 3845-3860 |
| PubMed ID | 28920922 | Mgi Jnum | J:247716 |
| Mgi Id | MGI:5926839 | Doi | 10.1172/JCI92067 |
| Citation | Koo JH, et al. (2017) Galpha13 ablation reprograms myofibers to oxidative phenotype and enhances whole-body metabolism. J Clin Invest 127(10):3845-3860 |
| abstractText | Skeletal muscle is a key organ in energy homeostasis owing to its high requirement for nutrients. Heterotrimeric G proteins converge signals from cell-surface receptors to potentiate or blunt responses against environmental changes. Here, we show that muscle-specific ablation of Galpha13 in mice promotes reprogramming of myofibers to the oxidative type, with resultant increases in mitochondrial biogenesis and cellular respiration. Mechanistically, Galpha13 and its downstream effector RhoA suppressed nuclear factor of activated T cells 1 (NFATc1), a chief regulator of myofiber conversion, by increasing Rho-associated kinase 2-mediated (Rock2-mediated) phosphorylation at Ser243. Ser243 phosphorylation of NFATc1 was reduced after exercise, but was higher in obese animals. Consequently, Galpha13 ablation in muscles enhanced whole-body energy metabolism and increased insulin sensitivity, thus affording protection from diet-induced obesity and hepatic steatosis. Our results define Galpha13 as a switch regulator of myofiber reprogramming, implying that modulations of Galpha13 and its downstream effectors in skeletal muscle are a potential therapeutic approach to treating metabolic diseases. |
