title: Activation of human stearoyl-coenzyme A desaturase 1 contributes to the lipogenic effect of PXR in HepG2 cells.
abstract: The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene.
authors.affiliation: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Yijuan
authors.initials: Y
authors.lastname: Wei
authors.forename: Bingfang
authors.initials: B
authors.lastname: Hu
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
authors.forename: Yonggong
authors.initials: Y
authors.lastname: Zhai
mesh_terms: D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D000077297:Pregnane X Receptor; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D012293:Rifampin / Q000494:pharmacology; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism*
chemical_list: D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; D012293:Rifampin