The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes.
Details
Serval ID
serval:BIB_9A257A1F04A8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes.
Journal
Nature communications
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
02/12/2021
Peer-reviewed
Oui
Volume
12
Number
1
Pages
7037
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
Growing evidence supports the importance of the p53 tumor suppressor in metabolism but the mechanisms underlying p53-mediated control of metabolism remain poorly understood. Here, we identify the multifunctional E4F1 protein as a key regulator of p53 metabolic functions in adipocytes. While E4F1 expression is upregulated during obesity, E4f1 inactivation in mouse adipose tissue results in a lean phenotype associated with insulin resistance and protection against induced obesity. Adipocytes lacking E4F1 activate a p53-dependent transcriptional program involved in lipid metabolism. The direct interaction between E4F1 and p53 and their co-recruitment to the Steaoryl-CoA Desaturase-1 locus play an important role to regulate monounsaturated fatty acids synthesis in adipocytes. Consistent with the role of this E4F1-p53-Steaoryl-CoA Desaturase-1 axis in adipocytes, p53 inactivation or diet complementation with oleate partly restore adiposity and improve insulin sensitivity in E4F1-deficient mice. Altogether, our findings identify a crosstalk between E4F1 and p53 in the control of lipid metabolism in adipocytes that is relevant to obesity and insulin resistance.
Keywords
Adipocytes/metabolism, Adipocytes/pathology, Adipose Tissue/metabolism, Adipose Tissue/pathology, Adult, Aged, Animals, Body Mass Index, Fatty Acids, Monounsaturated/metabolism, Female, Gene Expression Regulation, Humans, Insulin Resistance, Lipid Metabolism/genetics, Male, Mice, Mice, Knockout, Middle Aged, Obesity/genetics, Obesity/metabolism, Obesity/pathology, Repressor Proteins/deficiency, Repressor Proteins/genetics, Repressor Proteins/metabolism, Signal Transduction, Stearoyl-CoA Desaturase/genetics, Stearoyl-CoA Desaturase/metabolism, Tumor Suppressor Protein p53/genetics, Tumor Suppressor Protein p53/metabolism, Ubiquitin-Protein Ligases/deficiency, Ubiquitin-Protein Ligases/genetics, Ubiquitin-Protein Ligases/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
11/12/2021 12:49
Last modification date
08/08/2024 6:37