%0 Journal Article
%A Lacroix, Matthieu
%A Linares, Laetitia K
%A Rueda-Rincon, Natalia
%A Bloch, Katarzyna
%A Di Michele, Michela
%A De Blasio, Carlo
%A Fau, Caroline
%A Gayte, Laurie
%A Blanchet, Emilie
%A Mairal, Aline
%A Derua, Rita
%A Cardona, Fernando
%A Beuzelin, Diane
%A Annicotte, Jean-Sebastien
%A Pirot, Nelly
%A Torro, Adeline
%A Tinahones, Francisco J
%A Bernex, Florence
%A Bertrand-Michel, Justine
%A Langin, Dominique
%A Fajas, Lluis
%A Swinnen, Johannes V
%A Le Cam, Laurent
%T The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes.
%D 2021
%U https://hdl.handle.net/10668/26950
%X 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.
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