Lacroix, MatthieuLinares, Laetitia KRueda-Rincon, NataliaBloch, KatarzynaDi Michele, MichelaDe Blasio, CarloFau, CarolineGayte, LaurieBlanchet, EmilieMairal, AlineDerua, RitaCardona, FernandoBeuzelin, DianeAnnicotte, Jean-SebastienPirot, NellyTorro, AdelineTinahones, Francisco JBernex, FlorenceBertrand-Michel, JustineLangin, DominiqueFajas, LluisSwinnen, Johannes VLe Cam, Laurent2025-01-072025-01-072021-12-02https://hdl.handle.net/10668/26950Growing 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/AdipocytesAdipose TissueAdultAgedAnimalsBody Mass IndexFatty Acids, MonounsaturatedFemaleGene Expression RegulationHumansInsulin ResistanceLipid MetabolismMaleMiceMice, KnockoutMiddle AgedObesityRepressor ProteinsSignal TransductionStearoyl-CoA DesaturaseTumor Suppressor Protein p53Ubiquitin-Protein Ligasesresearch article34857760open access10.1038/s41467-021-27307-32041-1723PMC8639890https://www.nature.com/articles/s41467-021-27307-3.pdfhttps://pmc.ncbi.nlm.nih.gov/articles/PMC8639890/pdf