Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism.

Skeletal muscle is composed of both slow-twitch oxidative myofibers and fast-twitch glycolytic myofibers that differentially impact muscle metabolism, function and eventually whole-body physiology. Here we show that the mesodermal transcription factor T-box 15 (Tbx15) is highly and specifically expressed in glycolytic myofibers. Ablation of Tbx15 in vivo leads to a decrease in muscle size due to a decrease in the number of glycolytic fibres, associated with a small increase in the number of oxidative fibres. This shift in fibre composition results in muscles with slower myofiber contraction and relaxation, and also decreases whole-body oxygen consumption, reduces spontaneous activity, increases adiposity and glucose intolerance. Mechanistically, ablation of Tbx15 leads to activation of AMPK signalling and a decrease in Igf2 expression. Thus, Tbx15 is one of a limited number of transcription factors to be identified with a critical role in regulating glycolytic fibre identity and muscle metabolism.

Citation

Kevin Y Lee, Manvendra K Singh, Siegfried Ussar, Petra Wetzel, Michael F Hirshman, Laurie J Goodyear, Andreas Kispert, C Ronald Kahn. Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism. Nature communications. 2015;6:8054

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PMID: 26299309

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