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Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625615/ https://www.ncbi.nlm.nih.gov/pubmed/37925548 http://dx.doi.org/10.1038/s41467-023-43021-8 |
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author | Huang, Xun Li, Xinmeng Shen, Hongyu Zhao, Yiheng Zhou, Zhao Wang, Yushuang Yao, Jingfei Xue, Kaili Wu, Dongmei Qiu, Yifu |
author_facet | Huang, Xun Li, Xinmeng Shen, Hongyu Zhao, Yiheng Zhou, Zhao Wang, Yushuang Yao, Jingfei Xue, Kaili Wu, Dongmei Qiu, Yifu |
author_sort | Huang, Xun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10625615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106256152023-11-06 Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis Huang, Xun Li, Xinmeng Shen, Hongyu Zhao, Yiheng Zhou, Zhao Wang, Yushuang Yao, Jingfei Xue, Kaili Wu, Dongmei Qiu, Yifu Nat Commun Article 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. Nature Publishing Group UK 2023-11-04 /pmc/articles/PMC10625615/ /pubmed/37925548 http://dx.doi.org/10.1038/s41467-023-43021-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Huang, Xun Li, Xinmeng Shen, Hongyu Zhao, Yiheng Zhou, Zhao Wang, Yushuang Yao, Jingfei Xue, Kaili Wu, Dongmei Qiu, Yifu Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis |
title | Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis |
title_full | Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis |
title_fullStr | Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis |
title_full_unstemmed | Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis |
title_short | Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis |
title_sort | transcriptional repression of beige fat innervation via a yap/taz-s100b axis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625615/ https://www.ncbi.nlm.nih.gov/pubmed/37925548 http://dx.doi.org/10.1038/s41467-023-43021-8 |
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