RT Journal Article
T1 The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes
A1 Lacroix, Matthieu
A1 Linares, Laetitia K.
A1 Rueda-Rincon, Natalia
A1 Bloch, Katarzyna
A1 Di Michele, Michela
A1 De Blasio, Carlo
A1 Fau, Caroline
A1 Gayte, Laurie
A1 Blanchet, Emilie
A1 Mairal, Aline
A1 Derua, Rita
A1 Cardona, Fernando
A1 Beuzelin, Diane
A1 Annicotte, Jean-Sebastien
A1 Pirot, Nelly
A1 Torro, Adeline
A1 Tinahones, Francisco J.
A1 Bernex, Florence
A1 Bertrand-Michel, Justine
A1 Langin, Dominique
A1 Fajas, Lluis
A1 Swinnen, Johannes V.
A1 Le Cam, Laurent
K1 Transcription factor e4f1
K1 Cell-cycle arrest
K1 Growth
K1 Differentiation
K1 Identification
K1 Lipogenesis
K1 Activation
K1 Regulator
K1 P120(e4f)
K1 Reveals
AB 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.
PB Nature portfolio
YR 2021
FD 2021-12-02
LK https://hdl.handle.net/10668/26951
UL https://hdl.handle.net/10668/26951
LA en
DS RISalud
RD Apr 8, 2025