Dietary resveratrol increases the expression of hepatic 7α-hydroxylase and ameliorates hypercholesterolemia in high-fat fed C57BL/6J mice

Lipids in Health and Disease

Research

Qiong Chen¹  Pei Zhai¹  Liping Ma¹  Ermao Wang¹ 

[1] Department of food science, Guangdong Food and Drug Vocational College, 510635, Guangzhou, China;

关键词: Resveratrol;    High-fat diet;    LXRα;    Bile acid pool size;    Mice;   

DOI  :  10.1186/1476-511X-11-56

 received in 2012-04-04, accepted in 2012-05-02,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundResveratrol (RSV), a naturally occurring polyphenolic stilbenoid, is known to possess potent anti-atherogenic properties; however, the effect of RSV on hypercholesterolemia is not fully understood. We hypothesized that RSV decreases blood cholesterol levels through the activation of cholesterol 7α-hydroxylase (CYP7A1)-mediated bile acid synthetic pathway pathways in vitro and in vivo.MethodsIn this study, we evaluated body weight, serum lipid concentrations, hepatic lipid content and the size of the bile acid pool in high-fat diet (HFD)-fed C57BL/6 J mice that were treated with RSV. In addition, we characterized the underlying mechanism of the effects of RSV in HepG2 hepatocytes by Western blot analysis.ResultsRSV (200 mg/kg per day) reduced body weight and liver weight gains, improved serum lipid parameters, reduced hepatic cholesterol accumulation and increased the bile acid pool size in mice fed an HFD for 8 wks. RSV significantly increased liver expression of CYP7A1 mRNA and protein and CYP7A1 enzyme activity. Furthermore, RSV treatment upregulated CYP7A1 expression and induced liver X receptor alpha (LXRα) activation in a time- and dose-dependent manner in HepG2 cells. In addition, the specific liver X receptor alpha (LXRα) inhibitor geranylgeranyl pyrophosphate (GGPP) inhibited the RSV-induced expression of CYP7A1 in HepG2 hepatocytes.ConclusionThe beneficial effects of RSV on HFD-induced hypercholesterolemia are mediated through LXRα signaling pathways, suggesting a potential target for the prevention of dyslipidemia.

【 授权许可】

CC BY   
© Chen et al.; licensee BioMed Central Ltd. 2012