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Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis

Author

Listed:
  • Xun Huang

    (Peking University
    Peking University
    Peking University)

  • Xinmeng Li

    (Peking University)

  • Hongyu Shen

    (Peking University
    Peking University
    Peking University)

  • Yiheng Zhao

    (Peking University
    Peking University
    Peking University)

  • Zhao Zhou

    (Peking University)

  • Yushuang Wang

    (Peking University)

  • Jingfei Yao

    (Peking University)

  • Kaili Xue

    (Peking University)

  • Dongmei Wu

    (Peking University
    Peking University)

  • Yifu Qiu

    (Peking University
    Peking University)

Abstract

Sympathetic innervation is essential for the development of functional beige fat that maintains body temperature and metabolic homeostasis, yet the molecular mechanisms controlling this innervation remain largely unknown. Here, we show that adipocyte YAP/TAZ inhibit sympathetic innervation of beige fat by transcriptional repression of neurotropic factor S100B. Adipocyte-specific loss of Yap/Taz induces S100b expression to stimulate sympathetic innervation and biogenesis of functional beige fat both in subcutaneous white adipose tissue (WAT) and browning-resistant visceral WAT. Mechanistically, YAP/TAZ compete with C/EBPβ for binding to the zinc finger-2 domain of PRDM16 to suppress S100b transcription, which is released by adrenergic-stimulated YAP/TAZ phosphorylation and inactivation. Importantly, Yap/Taz loss in adipocytes or AAV-S100B overexpression in visceral WAT restricts both age-associated and diet-induced obesity, and improves metabolic homeostasis by enhancing energy expenditure of mice. Together, our data reveal that YAP/TAZ act as a brake on the beige fat innervation by blocking PRDM16-C/EBPβ-mediated S100b expression.

Suggested Citation

  • Xun Huang & Xinmeng Li & Hongyu Shen & Yiheng Zhao & Zhao Zhou & Yushuang Wang & Jingfei Yao & Kaili Xue & Dongmei Wu & Yifu Qiu, 2023. "Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43021-8
    DOI: 10.1038/s41467-023-43021-8
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