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

Xun Huang, Xinmeng Li, Hongyu Shen, Yiheng Zhao, Zhao Zhou, Yushuang Wang, Jingfei Yao, Kaili Xue, Dongmei Wu () and Yifu Qiu ()
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Xun Huang: Peking University
Xinmeng Li: Peking University
Hongyu Shen: Peking University
Yiheng Zhao: Peking University
Zhao Zhou: Peking University
Yushuang Wang: Peking University
Jingfei Yao: Peking University
Kaili Xue: Peking University
Dongmei Wu: Peking University
Yifu Qiu: Peking University

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43021-8

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