Effects of Bilberry Extract on Hepatic Cholesterol Metabolism in HepG2 Cells

Bilberry (Vaccinium myrtillus L.), rich in polyphenols, has been claimed to have lipid-lowering effects, but its underlying mechanisms remain unclear. The effects of bilberry extract (BE) with antioxidant properties on hepatic lipid metabolism were investigated by measuring the genes for cholesterol biosynthesis and flux in HepG2 cells. The mRNA and protein levels of genes involved in cholesterol biosynthesis such as sterol regulatory element-binding protein 2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase were decreased in BE-treated cells. BE posttranscriptionally upregulated low-density lipoprotein receptor in HepG2 cells. There was a marked reduction in genes for very low-density lipoprotein assembly by BE treatment. Furthermore, the expression of canalicular transporter for cholesterol and bile acids, such as ABCG8 and ABCB11, was significantly elevated by BE treatment. Downregulation of lipogenic genes and upregulation of fatty acid oxidation-related genes were observed in BE-treated HepG2 cells. The expressions of sirtuins were altered by BE treatment. These results support that the effects of BE on hepatic cholesterol metabolism may be attributed to the regulation of genes for hepatic cholesterol biosynthesis, transport and efflux