E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis.

Details

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Version: Supplementary document
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Serval ID
serval:BIB_D4C8969D5304
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis.
Journal
Journal of Clinical Investigation
Author(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
Publication state
Published
Issued date
2016
Volume
126
Number
1
Pages
137-150
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
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.
Keywords
Animals, Cyclin-Dependent Kinase 4/physiology, E2F1 Transcription Factor/physiology, Glycolysis, Humans, Lipogenesis, Liver/metabolism, Mice, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease/etiology, Response Elements, Sterol Regulatory Element Binding Protein 1/physiology
Pubmed
Web of science
Open Access
Yes
Create date
01/11/2016 22:58
Last modification date
01/08/2020 5:26
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