PPARγ overexpression regulates cholesterol metabolism in human L02 hepatocytes

Abstract Peroxisome proliferator-activator receptor (PPAR) γ is a nuclear hormone receptor that regulates glucose homeostasis, lipid metabolism, and adipocyte function. It has been shown that activation of PPARγ can reduce the incidence of gallstone. Herein we aimed to clarify the role of PPARγ in the reduction of gallstones. The plasmid containing the coding sequence of PPARγ was constructed and transfected in the human liver cell line (L02 cells). Western blot and RT-PCR were used to detect hydroxyl-methyl-glutaryl-CoA reductase (HMGCR), sterol regulatory element-binding proteins 2 (SREBP2), 7α-hydroxylase (CYP7A1), adenosine triphosphate-binding cassette (ABC) sterol transporters G5 and G8 (ABCG5, ABCG8) and liver X receptor α (LXRα). The Amplex Red cholesterol assay kit was used to detect the intracellular or extracellular cholesterol level. Our data showed that PPARγ overexpression caused significant decreases in both extracellular and intracellular cholesterol in the L02 cells. The further studies indicated PPARγ overexpression substantially decreased expression of HMGCR and SREBP-2, increased expression of CYP7A1, ABCG5, ABCG8 and LXRα. These results indicated that upregulation of PPARγ may reduce cholesterol levels through multiple-pathways including HMGCR/SREBP2-mediated biosynthesis, CYP7A1-mediated transformation, and ABCG5/ABCG8-mediated efflux. We thus suggest that PPARγ might have beneficial effects for cholesterol gallstones diseases.