G alpha 13 ablation reprograms myofibers to oxidative phenotype and enhances whole-body metabolism
- Authors
- Koo, Ja Hyun; Kim, Tae Hyun; Park, Shi-Young; Joo, Min Sung; Han, Chang Yeob; Choi, Cheol Soo; Kim, Sang Geon
- Issue Date
- 2-Oct-2017
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC
- Citation
- JOURNAL OF CLINICAL INVESTIGATION, v.127, no.10, pp.3845 - 3860
- Journal Title
- JOURNAL OF CLINICAL INVESTIGATION
- Volume
- 127
- Number
- 10
- Start Page
- 3845
- End Page
- 3860
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/5591
- DOI
- 10.1172/JCI92067
- ISSN
- 0021-9738
- 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 G alpha 13 in mice promotes reprogramming of myofibers to the oxidative type, with resultant increases in mitochondrial biogenesis and cellular respiration. Mechanistically, G alpha 13 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, G alpha 13 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 G alpha 13 as a switch regulator of myofiber reprogramming, implying that modulations of G alpha 13 and its downstream effectors in skeletal muscle are a potential therapeutic approach to treating metabolic diseases.
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