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YAP and TAZ protect against white adipocyte cell death during obesity

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Item Type:Article
Title:YAP and TAZ protect against white adipocyte cell death during obesity
Creators Name:Wang, L. and Wang, S.P. and Shi, Y. and Li, R. and Günther, S. and Ong, Y.T. and Potente, M. and Yuan, Z. and Liu, E. and Offermanns, S.
Abstract: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.
Keywords:Adipogenesis, Animal Disease Models, Bcl-2-Like Protein 11, Cell Cycle Proteins, Cell Death, Cultured Cells, Gene Expression Regulation, High-Fat Diet, Inbred C57BL Mice, Knockout Mice, Obesity, Signal Transducing Adaptor Proteins, Trans-Activators, Transcription Factors, White Adipocytes, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:5455
Date:28 October 2020
Official Publication:https://doi.org/10.1038/s41467-020-19229-3
PubMed:View item in PubMed

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