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

Abstract

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.

Nutraceuticals and dyslipidaemia: Beyond the common therapeutics

“…Bile acids genesis contributes to the elimination of cholesterol from plasma. Chen et al (2012) demonstrated increased CYP7A1 mRNA transcription, protein production and activity. In particular, CYP7A1 increased liver X receptor alpha (LXRa) activation.…”

“…The benefits from red wine consumption (i.e., the ''French paradox'') (Renaud & de Lorgeril, 1992) higher concentrations of resveratrol are in red wine (0.847 mg/100 g) and itadori tea (0.974 mg/100 g), followed by wine, grapes, grape juice and peanut butter (range from 0.08 to 0.547 mg/100 g) and peanuts, pistachios and berries (0.01 mg/100 g). Chen et al (2012) hypothesised the role of resveratrol in counteracting hypercholesterolaemia. They fed mice a hypercholesterolaemic diet and resveratrol (200 mg/kg/day) for 8 weeks, observing a reduction in main serum lipid parameters.…”

“…Functional food ingredients can act on several biochemical pathways able to influence lipid disorders in the human body. Physicians have attempted to identify the mechanisms responsible for nutraceuticals actions (Baiges et al, 2010;Chen et al, 2012;Kato et al, 2009;Quesada et al, 2009Quesada et al, , 2012. The benefits from red wine consumption (i.e., the ''French paradox'') (Renaud & de Lorgeril, 1992) higher concentrations of resveratrol are in red wine (0.847 mg/100 g) and itadori tea (0.974 mg/100 g), followed by wine, grapes, grape juice and peanut butter (range from 0.08 to 0.547 mg/100 g) and peanuts, pistachios and berries (0.01 mg/100 g).…”

High Dietary Selenium Intake Alters Lipid Metabolism and Protein Synthesis in Liver and Muscle of Pigs

“…Dietary selenium and/or GPX1 production (9) affected the functional expression of important proteins involved in gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK)] and glycolysis [glucokinase (GK)] (10), insulin signaling [insulin receptor (INSR), insulin receptor substrate 1 (IRS1), and v-akt murine thymoma viral oncogene homolog 2 (AKT2)], and lipid metabolism (11) [sterol regulatory element binding protein (SREBP) 1 and SREBP2, acetyl-CoA carboxylase 1 (ACC1); cholesterol 7a-hydroxylase (CYP7A1), PPARG, fatty acid synthase (FASN), and tumor suppressor p53 (P53)] (12)(13)(14)(15)(16)(17). Alterations of these factors were associated with expressions of 12 selenoproteins (1,3,5,9,18,19).…”

Nutraceuticals in Dyslipidemia: An Alternative Approach

“…It mediates the conversion of cholesterol in 7α-hydroxycholesterol and, subsequently, in cholic acid. Bile acids genesis contributes to the elimination of cholesterol from plasma [25].…”