Nature communications, 2021-12, Vol.12 (1), p.7037-7037, Article 7037
- 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
- Fajas, Lluis
- Swinnen, Johannes V.
- Le Cam, Laurent
2021
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- Autor(en) / Beteiligte
- 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
- Fajas, Lluis
- Swinnen, Johannes V.
- Le Cam, Laurent
- Titel
- The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes
- Ist Teil von
- Nature communications, 2021-12, Vol.12 (1), p.7037-7037, Article 7037
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2021
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-021-27307-3Titel-ID: cdi_doaj_primary_oai_doaj_org_article_00ec515c8ba444a682cea51127843aeb
- Format
- –
- Schlagworte
- 13/51, 13/89, 38/15, 38/62, 38/77, 38/88, 38/90, 45/15, 45/22, 631/337/572, 631/443/319/2723, 64/110, 692/163/2743/393, Adipocytes, Adipocytes - metabolism, Adipocytes - pathology, Adipose tissue, Adipose Tissue - metabolism, Adipose Tissue - pathology, Adult, Aged, Animal tissues, Animals, Body Mass Index, Crosstalk, Deactivation, Desaturase, Diet, Endocrinology and metabolism, Fatty acids, Fatty Acids, Monounsaturated - metabolism, Female, Gene Expression Regulation, Human health and pathology, Humanities and Social Sciences, Humans, Inactivation, Insulin, Insulin Resistance, Life Sciences, Lipid metabolism, Lipid Metabolism - genetics, Lipids, Male, Metabolism, Mice, Mice, Knockout, Middle Aged, multidisciplinary, Obesity, Obesity - genetics, Obesity - metabolism, Obesity - pathology, p53 Protein, Phenotypes, Protein turnover, Proteins, Repressor Proteins - deficiency, Repressor Proteins - genetics, Repressor Proteins - metabolism, Science, Science (multidisciplinary), Signal Transduction, Stearoyl-CoA Desaturase - genetics, Stearoyl-CoA Desaturase - metabolism, Transcription, Tumor suppressor genes, Tumor Suppressor Protein p53 - genetics, Tumor Suppressor Protein p53 - metabolism, Tumors, Ubiquitin-Protein Ligases - deficiency, Ubiquitin-Protein Ligases - genetics, Ubiquitin-Protein Ligases - metabolism