title: 20(S)-protopanaxatriol inhibits liver X receptor α-mediated expression of lipogenic genes in hepatocytes.
abstract: 20(S)-protopanaxatriol (PPT) is an aglycone of ginsenosides isolated from Panax ginseng and has several interesting activities, including anti-inflammatory and anti-oxidative stress effects. Herein, PPT was identified as an inhibitor against the ligand-dependent transactivation of liver X receptor α (LXRα) using a Gal4-TK-luciferase reporter system. LXRα is a transcription factor of nuclear hormone receptor family and stimulates the transcription of many metabolic genes, such as lipogenesis- or reverse cholesterol transport (RCT)-related genes. Quantitative RT-PCR analysis showed that PPT inhibited the LXRα-dependent transcription of lipogenic genes, such as sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase, and stearoyl CoA desaturase 1. These inhibitory effects of PPT are, at least in part, a consequence of the reduced recruitment of RNA polymerase II to the LXR response element (LXRE) of the SREBP-1c promoter. Furthermore, LXRα-dependent triglyceride accumulation in primary mouse hepatocytes was significantly reduced by PPT. Interestingly, PPT did not inhibit the LXRα-dependent transcription of ABCA1, a crucial LXRα target gene involved in RCT. Chromatin immunoprecipitation assays revealed that PPT repressed recruitment of the lipogenic coactivator TRAP80 to the SREBP-1c LXRE, but not the ABCA1 LXRE. Overall, these data suggest that PPT has selective inhibitory activity against LXRα-mediated lipogenesis, but not LXRα-stimulated RCT.
authors.affiliation: Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Bio-medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Gyun-Sik
authors.initials: GS
authors.lastname: Oh
authors.affiliation: Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Bio-medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Yoon
authors.affiliation: Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Bio-medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Gang Gu
authors.initials: GG
authors.lastname: Lee
authors.affiliation: Korea Bioactive Natural Material Bank, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Won Keun
authors.initials: WK
authors.lastname: Oh
authors.affiliation: Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Bio-medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea. Electronic address: swkim7@amc.seoul.kr.
authors.forename: Seung-Whan
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism*; D050155:Lipogenesis / Q000187:drug effects* / Q000235:genetics*; D000071518:Liver X Receptors; D008297:Male; D056892:Mediator Complex / Q000378:metabolism; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors* / Q000502:physiology; D012502:Sapogenins / Q000494:pharmacology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D036145:Ginsenosides; D000071518:Liver X Receptors; C538713:Med17 protein, human; D056892:Mediator Complex; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D012502:Sapogenins; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; C507965:ginsenoside 20S-protopanaxatriol; D002784:Cholesterol
keywords: 20(S)-protopanaxatriol; Lipogenesis; Liver X receptor α; Steatosis; Sterol-regulatory element binding protein-1c