PPARγ overexpression regulates cholesterol metabolism in human L02 hepatocytes

Peroxisome proliferator-activator receptor (PPAR) gamma is a nuclear hormone receptor that regulates glucose homeostasis, lipid metabolism, and adipocyte function. It has been shown that activation of PPAR gamma can reduce the incidence of gallstone. Herein we aimed to clarify the role of PPAR gamma in the reduction of gallstones. The plasmid containing the coding sequence of PPAR gamma 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), 7 alpha-hydroxylase (CYP7A1), adenosine triphosphate-binding cassette (ABC) sterol transporters G5 and G8 (ABCG5, ABCG8) and liver X receptor alpha (LXR alpha). The Amplex Red cholesterol assay kit was used to detect the intracellular or extracellular cholesterol level. Our data showed that PPAR gamma overexpression caused significant decreases in both extracellular and intracellular cholesterol in the L02 cells. The further studies indicated PPAR gamma overexpression substantially decreased expression of HMGCR and SREBP-2, increased expression of CYP7A1, ABCG5, ABCG8 and LXR alpha. These results indicated that upregulation of PPAR gamma may reduce cholesterol levels through multiple-pathways including HMGCR/SREBP2-mediated biosynthesis, CYP7A1-mediated transformation, and ABCG5/ABCG8-mediated efflux. We thus suggest that PPAR gamma might have beneficial effects for cholesterol gallstones diseases. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).