The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_9A257A1F04A8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes.
Périodique
Nature communications
Auteur⸱e⸱s
Lacroix M., Linares L.K., Rueda-Rincon N., Bloch K., Di Michele M., De Blasio C., Fau C., Gayte L., Blanchet E., Mairal A., Derua R., Cardona F., Beuzelin D., Annicotte J.S., Pirot N., Torro A., Tinahones F.J., Bernex F., Bertrand-Michel J., Langin D., Fajas L., Swinnen J.V., Le Cam L.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
02/12/2021
Peer-reviewed
Oui
Volume
12
Numéro
1
Pages
7037
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
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.
Mots-clé
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
Oui
Création de la notice
11/12/2021 12:49
Dernière modification de la notice
08/08/2024 6:37
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