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

• Published in: Nature communications Vol. 14; no. 1; p. 7102
• Main Authors: Huang, Xun, Li, Xinmeng, Shen, Hongyu, Zhao, Yiheng, Zhou, Zhao, Wang, Yushuang, Yao, Jingfei, Xue, Kaili, Wu, Dongmei, Qiu, Yifu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-11-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/31; 13/44; 13/51; 13/95; 14/19; 38/15; 38/90; 38/91; 45; 631/443/319; 631/80/304; 64; 64/60; 692/699/317; Adipocytes; Adipose tissue; Body temperature; Brakes; Energy expenditure; Gene silencing; Homeostasis; Humanities and Social Sciences; Inactivation; Innervation; Metabolism; Molecular modelling; multidisciplinary; Phosphorylation; S100b protein; Science; Science (multidisciplinary); Zinc finger proteins
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43021-8

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.
Sympathetic innervation is essential for the development of functional beige fat that maintains metabolic homeostasis. Qiu and colleagues discover that YAP/TAZ can act as a brake on the beige fat innervation by blocking PRDM16-C/EBPβ-mediated S100b expression.