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Nat Commun. 2015 Aug 24;6:8054. doi: 10.1038/ncomms9054.

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

Author information

1
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Plaza, Boston, Massachusetts 02215, USA.
2
Institut für Molekularbiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
3
Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School Singapore, National Heart Centre Singapore, 8 College Road, Singapore 169857, Singapore.
4
Institute for Diabetes and Obesity, Helmholtz Center, Parkring, 1385748 Munich/Garching, Germany.
5
Zentrum Physiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.

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.

PMID:
26299309
PMCID:
PMC4552045
DOI:
10.1038/ncomms9054
[Indexed for MEDLINE]
Free PMC Article

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