Lee, Kevin Y.Singh, Manvendra K.Ussar, SiegfriedWetzel, PetraHirshman, Michael F.Goodyear, LaurieKispert, AndreasKahn, C.2015-10-012015Lee, Kevin Y., Manvendra K. Singh, Siegfried Ussar, Petra Wetzel, Michael F. Hirshman, Laurie J. Goodyear, Andreas Kispert, and C. Ronald Kahn. 2015. “Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism.” Nature Communications 6 (1): 8054. doi:10.1038/ncomms9054. http://dx.doi.org/10.1038/ncomms9054.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:22857014Skeletal 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.en-USJournal Article2015-10-0110.1038/ncomms9054