%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/10668/26951
%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.The p53 tumor suppressor is also a regulator of metabolism, but the mechanisms controlling p53-associated metabolic activities remain poorly understood. Here the authors report that the deletion of the multifunctional protein E4F1 is protective against diet-induced obesity in mice, and E4F1 regulates adipocyte lipid metabolism through p53.
%K Transcription factor e4f1
%K Cell-cycle arrest
%K Growth
%K Differentiation
%K Identification
%K Lipogenesis
%K Activation
%K Regulator
%K P120(e4f)
%K Reveals
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