Resveratrol increases the expression and activity of the low density lipoprotein receptor in hepatocytes by the proteolytic activation of the sterol regulatory element-binding proteins.
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Yashiro T, Nanmoku M, Shimizu M, Inoue J, Sato R
Resveratrol increases the expression and activity of the low density lipoprotein receptor in hepatocytes by the proteolytic activation of the sterol regulatory element-binding proteins.
Atherosclerosis. 2012 Feb;220(2):369-74. doi: 10.1016/j.atherosclerosis.2011.11.006. Epub 2011 Nov 16.
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- 22153697 [ View in PubMed]
- Abstract
OBJECTIVE: The hepatocyte low density lipoprotein receptor (LDLR) plays a pivotal role in lipoprotein metabolism by lowering plasma LDL-cholesterol, a risk factor for atherosclerosis. The present study was conducted to investigate the effects of grape polyphenols on LDLR gene expression in human hepatocyte models. METHODS AND RESULTS: Among the 14 phenolic compounds in red wine, we found that a stilbene trans-resveratrol most strongly up-regulated LDLR gene expression in HepG2 cells. Trans-resveratrol increased the LDLR protein and uptake of fluorescent-labeled LDL. Moreover, it enhanced LDLR gene promoter activity through the proteolytic activation of the sterol regulatory element-binding protein-2 (SREBP-2) as well as SREBP-1. However, sterols completely abolished trans-resveratrol-induced SREBP activation and LDLR gene expression. Finally, AMP-activated protein kinase (AMPK) knockdown analyses by siRNA revealed that AMPK activation was unnecessary for the effects of trans-resveratrol. CONCLUSIONS: Trans-resveratrol up-regulated hepatic LDLR expression via proteolytic activation of SREBPs. We concluded that trans-resveratrol exhibits the anti-atherogenic effect, at least in part, by increased hepatic LDLR expression and subsequent LDL uptake.