Usage Information

E2F1 inhibits circulating cholesterol clearance by regulating Pcsk9 expression in the liver
Qiuwen Lai, Albert Giralt, Cédric Le May, Lianjun Zhang, Bertrand Cariou, Pierre-Damien Denechaud, Lluis Fajas
Qiuwen Lai, Albert Giralt, Cédric Le May, Lianjun Zhang, Bertrand Cariou, Pierre-Damien Denechaud, Lluis Fajas
View: Text | PDF
Research Article Hepatology Metabolism

E2F1 inhibits circulating cholesterol clearance by regulating Pcsk9 expression in the liver

Abstract

Cholesterol accumulation in the liver is an early event in nonalcoholic fatty liver disease (NAFLD). Here, we demonstrate that E2F1 plays a crucial role in maintaining cellular cholesterol homeostasis by regulating cholesterol uptake via proprotein convertase subtilisin/kexin 9 (PCSK9), an enzyme that promotes low-density lipoprotein receptor (LDLR) degradation upon activation. E2f1–/– mice display reduced total plasma cholesterol levels and increased cholesterol content in the liver. In this study, we show that E2f1 deletion in cellular and mouse models leads to a marked decrease in Pcsk9 expression and an increase in LDLR expression. In addition to the upregulation of LDLR, we report that E2f1–/– hepatocytes exhibit increased LDL uptake. ChIP-Seq and PCSK9 promoter reporter experiments confirmed that E2F1 binds to and transactivates the PCSK9 promoter. Interestingly, E2f1–/– mice fed a high-cholesterol diet (HCD) display a fatty liver phenotype and liver fibrosis, which is reversed by reexpression of PCSK9 in the liver. Collectively, these data indicate that E2F1 regulates cholesterol uptake and that the loss of E2F1 leads to abnormal cholesterol accumulation in the liver and the development of fibrosis in response to an HCD.

Authors

Qiuwen Lai, Albert Giralt, Cédric Le May, Lianjun Zhang, Bertrand Cariou, Pierre-Damien Denechaud, Lluis Fajas

×

Usage data is cumulative from December 2024 through December 2025.

Usage JCI PMC
Text version 514 125
PDF 122 39
Figure 506 7
Table 52 0
Supplemental data 42 7
Citation downloads 122 0
Totals 1,358 178
Total Views 1,536
(Click and drag on plot area to zoom in. Click legend items above to toggle)

Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.

Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.

Advertisement