The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes.
Nat Commun
; 12(1): 7037, 2021 12 02.
Article
em En
| MEDLINE
| ID: mdl-34857760
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Estearoil-CoA Dessaturase
/
Tecido Adiposo
/
Proteína Supressora de Tumor p53
/
Adipócitos
/
Ubiquitina-Proteína Ligases
/
Obesidade
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França