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Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism

Author

Listed:
  • 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
    Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School Singapore, National Heart Centre Singapore, 8 College Road)

  • Siegfried Ussar

    (Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Plaza
    Institute for Diabetes and Obesity, Helmholtz Center, Parkring)

  • 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)

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.

Suggested Citation

  • Kevin Y. Lee & Manvendra K. Singh & Siegfried Ussar & Petra Wetzel & Michael F. Hirshman & Laurie J. Goodyear & Andreas Kispert & C. Ronald Kahn, 2015. "Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9054
    DOI: 10.1038/ncomms9054
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    Cited by:

    1. Peter T. Ajayi & Prasanna Katti & Yingfan Zhang & T. Bradley Willingham & Ye Sun & Christopher K. E. Bleck & Brian Glancy, 2022. "Regulation of the evolutionarily conserved muscle myofibrillar matrix by cell type dependent and independent mechanisms," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Likun Yang & Lin Liu & Wen Wang & Chenyun Ding & Aneesh K. Asokan & Tingze Feng & Danxia Zhou & Zhisheng Xu & Tingting Fu & Qiqi Guo & Zheng Zhou & Shaojun Pei & Gonghao Shen & Liwei Xiao & Yujing Yin, 2025. "Enhancer regulator MLL4 controls skeletal muscle metabolic efficiency by limiting AMPK-mediated fuel catabolism," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    3. Zheng Zhou & Lin Liu & Zhisheng Xu & Danxia Zhou & Anqi Liu & Jiachen Yuan & Gonghao Shen & Qiqi Guo & Yujing Yin & Yan Mao & Wanping Sun & Liwei Xiao & Cheng Lv & Abdukahar Kiram & Likun Yang & Yuhua, 2026. "BRD4 directs myofiber identity and metabolic adaptation through CHD4 cooperation," Nature Communications, Nature, vol. 17(1), pages 1-21, December.

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