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G?13 ablation reprograms myofibers to oxidative phenotype and enhances whole-body metabolism.

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?13 in mice promotes reprogramming of myofibers to the oxidative type, with resultant increases in mitochondrial biogenesis and cellular respiration. Mechanistically, G?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?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?13 as a switch regulator of myofiber reprogramming, implying that modulations of G?13 and its downstream effectors in skeletal muscle are a potential therapeutic approach to treating metabolic diseases.

SUBMITTER: Koo JH

PROVIDER: S-EPMC5617657 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Gα13 ablation reprograms myofibers to oxidative phenotype and enhances whole-body metabolism.

Koo Ja Hyun JH Kim Tae Hyun TH Park Shi-Young SY Joo Min Sung MS Han Chang Yeob CY Choi Cheol Soo CS Kim Sang Geon SG

The Journal of clinical investigation 20170918 10

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 nuc ...[more]

PMID: 28920922

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Dataset Information

G?13 ablation reprograms myofibers to oxidative phenotype and enhances whole-body metabolism.

Publications

Gα13 ablation reprograms myofibers to oxidative phenotype and enhances whole-body metabolism.

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