Cargando…

YAP and TAZ protect against white adipocyte cell death during obesity

The expansion of the white adipose tissue (WAT) in obesity goes along with increased mechanical, metabolic and inflammatory stress. How adipocytes resist this stress is still poorly understood. Both in human and mouse adipocytes, the transcriptional co-activators YAP/TAZ and YAP/TAZ target genes bec...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Lei, Wang, ShengPeng, Shi, Yue, Li, Rui, Günther, Stefan, Ong, Yu Ting, Potente, Michael, Yuan, Zuyi, Liu, Enqi, Offermanns, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595161/
https://www.ncbi.nlm.nih.gov/pubmed/33116140
http://dx.doi.org/10.1038/s41467-020-19229-3
_version_ 1783601803354439680
author Wang, Lei
Wang, ShengPeng
Shi, Yue
Li, Rui
Günther, Stefan
Ong, Yu Ting
Potente, Michael
Yuan, Zuyi
Liu, Enqi
Offermanns, Stefan
author_facet Wang, Lei
Wang, ShengPeng
Shi, Yue
Li, Rui
Günther, Stefan
Ong, Yu Ting
Potente, Michael
Yuan, Zuyi
Liu, Enqi
Offermanns, Stefan
author_sort Wang, Lei
collection PubMed
description The expansion of the white adipose tissue (WAT) in obesity goes along with increased mechanical, metabolic and inflammatory stress. How adipocytes resist this stress is still poorly understood. Both in human and mouse adipocytes, the transcriptional co-activators YAP/TAZ and YAP/TAZ target genes become activated during obesity. When fed a high-fat diet (HFD), mice lacking YAP/TAZ in white adipocytes develop severe lipodystrophy with adipocyte cell death. The pro-apoptotic factor BIM, which is downregulated in adipocytes of obese mice and humans, is strongly upregulated in YAP/TAZ-deficient adipocytes under HFD, and suppression of BIM expression reduces adipocyte apoptosis. In differentiated adipocytes, TNFα and IL-1β promote YAP/TAZ nuclear translocation via activation of RhoA-mediated actomyosin contractility and increase YAP/TAZ-mediated transcriptional regulation by activation of c-Jun N-terminal kinase (JNK) and AP-1. Our data indicate that the YAP/TAZ signaling pathway may be a target to control adipocyte cell death and compensatory adipogenesis during obesity.
format Online
Article
Text
id pubmed-7595161
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-75951612020-11-10 YAP and TAZ protect against white adipocyte cell death during obesity Wang, Lei Wang, ShengPeng Shi, Yue Li, Rui Günther, Stefan Ong, Yu Ting Potente, Michael Yuan, Zuyi Liu, Enqi Offermanns, Stefan Nat Commun Article The expansion of the white adipose tissue (WAT) in obesity goes along with increased mechanical, metabolic and inflammatory stress. How adipocytes resist this stress is still poorly understood. Both in human and mouse adipocytes, the transcriptional co-activators YAP/TAZ and YAP/TAZ target genes become activated during obesity. When fed a high-fat diet (HFD), mice lacking YAP/TAZ in white adipocytes develop severe lipodystrophy with adipocyte cell death. The pro-apoptotic factor BIM, which is downregulated in adipocytes of obese mice and humans, is strongly upregulated in YAP/TAZ-deficient adipocytes under HFD, and suppression of BIM expression reduces adipocyte apoptosis. In differentiated adipocytes, TNFα and IL-1β promote YAP/TAZ nuclear translocation via activation of RhoA-mediated actomyosin contractility and increase YAP/TAZ-mediated transcriptional regulation by activation of c-Jun N-terminal kinase (JNK) and AP-1. Our data indicate that the YAP/TAZ signaling pathway may be a target to control adipocyte cell death and compensatory adipogenesis during obesity. Nature Publishing Group UK 2020-10-28 /pmc/articles/PMC7595161/ /pubmed/33116140 http://dx.doi.org/10.1038/s41467-020-19229-3 Text en © The Author(s) 2020 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Lei
Wang, ShengPeng
Shi, Yue
Li, Rui
Günther, Stefan
Ong, Yu Ting
Potente, Michael
Yuan, Zuyi
Liu, Enqi
Offermanns, Stefan
YAP and TAZ protect against white adipocyte cell death during obesity
title YAP and TAZ protect against white adipocyte cell death during obesity
title_full YAP and TAZ protect against white adipocyte cell death during obesity
title_fullStr YAP and TAZ protect against white adipocyte cell death during obesity
title_full_unstemmed YAP and TAZ protect against white adipocyte cell death during obesity
title_short YAP and TAZ protect against white adipocyte cell death during obesity
title_sort yap and taz protect against white adipocyte cell death during obesity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595161/
https://www.ncbi.nlm.nih.gov/pubmed/33116140
http://dx.doi.org/10.1038/s41467-020-19229-3
work_keys_str_mv AT wanglei yapandtazprotectagainstwhiteadipocytecelldeathduringobesity
AT wangshengpeng yapandtazprotectagainstwhiteadipocytecelldeathduringobesity
AT shiyue yapandtazprotectagainstwhiteadipocytecelldeathduringobesity
AT lirui yapandtazprotectagainstwhiteadipocytecelldeathduringobesity
AT guntherstefan yapandtazprotectagainstwhiteadipocytecelldeathduringobesity
AT ongyuting yapandtazprotectagainstwhiteadipocytecelldeathduringobesity
AT potentemichael yapandtazprotectagainstwhiteadipocytecelldeathduringobesity
AT yuanzuyi yapandtazprotectagainstwhiteadipocytecelldeathduringobesity
AT liuenqi yapandtazprotectagainstwhiteadipocytecelldeathduringobesity
AT offermannsstefan yapandtazprotectagainstwhiteadipocytecelldeathduringobesity