E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis.

Détails

ID Serval
serval:BIB_3AE623148174
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis.
Périodique
Journal of Clinical Investigation
Auteur(s)
Denechaud P.D., Lopez-Mejia I.C., Giralt A., Lai Q., Blanchet E., Delacuisine B., Nicolay B.N., Dyson N.J., Bonner C., Pattou F., Annicotte J.S., Fajas L.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
2016
Volume
126
Numéro
1
Pages
137-150
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
E2F transcription factors are known regulators of the cell cycle, proliferation, apoptosis, and differentiation. Here, we reveal that E2F1 plays an essential role in liver physiopathology through the regulation of glycolysis and lipogenesis. We demonstrate that E2F1 deficiency leads to a decrease in glycolysis and de novo synthesis of fatty acids in hepatocytes. We further demonstrate that E2F1 directly binds to the promoters of key lipogenic genes, including Fasn, but does not bind directly to genes encoding glycolysis pathway components, suggesting an indirect effect. In murine models, E2F1 expression and activity increased in response to feeding and upon insulin stimulation through canonical activation of the CDK4/pRB pathway. Moreover, E2F1 expression was increased in liver biopsies from obese, glucose-intolerant humans compared with biopsies from lean subjects. Finally, E2f1 deletion completely abrogated hepatic steatosis in different murine models of nonalcoholic fatty liver disease (NAFLD). In conclusion, our data demonstrate that E2F1 regulates lipid synthesis and glycolysis and thus contributes to the development of liver pathology.
Pubmed
Open Access
Oui
Création de la notice
07/01/2016 12:04
Dernière modification de la notice
21/08/2019 6:33
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