Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism

Kevin Y. Lee, Manvendra K. Singh, Siegfried Ussar, Petra Wetzel, Michael F. Hirshman, Laurie J. Goodyear, Andreas Kispert and C. Ronald Kahn ()
Additional contact information
Kevin Y. Lee: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Plaza
Manvendra K. Singh: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625
Siegfried Ussar: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Plaza
Petra Wetzel: Zentrum Physiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625
Michael F. Hirshman: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Plaza
Laurie J. Goodyear: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Plaza
Andreas Kispert: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625
C. Ronald Kahn: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Plaza

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms9054

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