The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes.
Adipocytes
/ metabolism
Adipose Tissue
/ metabolism
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
Repressor Proteins
/ deficiency
Signal Transduction
Stearoyl-CoA Desaturase
/ genetics
Tumor Suppressor Protein p53
/ genetics
Ubiquitin-Protein Ligases
/ deficiency
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 12 2021
02 12 2021
Historique:
received:
12
08
2016
accepted:
12
11
2021
entrez:
3
12
2021
pubmed:
4
12
2021
medline:
5
1
2022
Statut:
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.
Identifiants
pubmed: 34857760
doi: 10.1038/s41467-021-27307-3
pii: 10.1038/s41467-021-27307-3
pmc: PMC8639890
doi:
Substances chimiques
Fatty Acids, Monounsaturated
0
Repressor Proteins
0
Tumor Suppressor Protein p53
0
Stearoyl-CoA Desaturase
EC 1.14.19.1
E4F1 protein, human
EC 2.3.2.27
E4f1 protein, mouse
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7037Informations de copyright
© 2021. The Author(s).
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