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- Title
Gα13 ablation reprograms myofibers to oxidative phenotype and enhances whole-body metabolism.
- Authors
Ja Hyun Koo; Tae Hyun Kim; Shi-Young Park; Min Sung Joo; Chang Yeob Han; Cheol Soo Choi; Sang Geon Kim; Koo, Ja Hyun; Kim, Tae Hyun; Park, Shi-Young; Joo, Min Sung; Han, Chang Yeob; Choi, Cheol Soo; Kim, Sang Geon
- Abstract
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 Gα13 in mice promotes reprogramming of myofibers to the oxidative type, with resultant increases in mitochondrial biogenesis and cellular respiration. Mechanistically, Gα13 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, Gα13 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 Gα13 as a switch regulator of myofiber reprogramming, implying that modulations of Gα13 and its downstream effectors in skeletal muscle are a potential therapeutic approach to treating metabolic diseases.
- Subjects
SKELETAL muscle; HOMEOSTASIS; G proteins; MITOCHONDRIA formation; CELL membrane formation; LABORATORY mice; METABOLIC disorder treatment
- Publication
Journal of Clinical Investigation, 2017, Vol 127, Issue 10, p3845
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI92067