title: Dietary resveratrol increases the expression of hepatic 7α-hydroxylase and ameliorates hypercholesterolemia in high-fat fed C57BL/6J mice.
abstract: BACKGROUND
  Resveratrol (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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  RSV (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.
  
  
  CONCLUSIONS
  The beneficial effects of RSV on HFD-induced hypercholesterolemia are mediated through LXRα signaling pathways, suggesting a potential target for the prevention of dyslipidemia.
authors.affiliation: Department of food science, Guangdong Food and Drug Vocational College, Guangzhou, 510635, China. chenqiong307@163.com
authors.forename: Qiong
authors.initials: Q
authors.lastname: Chen
authors.forename: Ermao
authors.initials: E
authors.lastname: Wang
authors.forename: Liping
authors.initials: L
authors.lastname: Ma
authors.forename: Pei
authors.initials: P
authors.lastname: Zhai
mesh_terms: D000818:Animals; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D019587:Dietary Supplements; D056945:Hep G2 Cells; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000209:etiology; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008099:Liver / Q000201:enzymology*; D000071518:Liver X Receptors; D051379:Mice; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D000960:Hypolipidemic Agents; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D013267:Stilbenes; D002790:Cholesterol 7-alpha-Hydroxylase; C502772:Cyp7a1 protein, mouse; D000077185:Resveratrol