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- Title
The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes.
- Authors
Lacroix, Matthieu; Linares, Laetitia K.; Rueda-Rincon, Natalia; Bloch, Katarzyna; Di Michele, Michela; De Blasio, Carlo; Fau, Caroline; Gayte, Laurie; Blanchet, Emilie; Mairal, Aline; Derua, Rita; Cardona, Fernando; Beuzelin, Diane; Annicotte, Jean-Sebastien; Pirot, Nelly; Torro, Adeline; Tinahones, Francisco J.; Bernex, Florence; Bertrand-Michel, Justine; Langin, Dominique
- 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. 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.
- Subjects
FAT cells; LIPID metabolism; ADIPOSE tissue physiology; INSULIN sensitivity; METABOLIC regulation; INSULIN resistance; MONOUNSATURATED fatty acids; P53 protein
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-27307-3