title: Ethyl 2,4,6-trihydroxybenzoate is an agonistic ligand for liver X receptor that induces cholesterol efflux from macrophages without affecting lipid accumulation in HepG2 cells.
abstract: The present study reports a novel liver X receptor (LXR) activator, ethyl 2,4,6-trihydroxybenzoate (ETB), isolated from Celtis biondii. Using a reporter gene assay, time-resolved fluorescence resonance energy transfer (TR-FRET), and surface plasmon resonance (SPR) analysis, we showed that ETB directly bound to and stimulated the transcriptional activity of LXR-α and LXR-β. In macrophages, hepatocytes, and intestinal cells, ETB suppressed cellular cholesterol accumulation in a dose-dependent manner and induced the transcriptional activation of LXR-α/-β-responsive genes. Notably, ETB did not induce lipogenic gene expression or cellular triglyceride accumulation in hepatocytes. These results suggest that ETB is a dual-LXR modulator that regulates the expression of key genes in cholesterol homeostasis in multiple cells without inducing lipid accumulation in HepG2 cells.
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, South Korea.
authors.forename: Minh-Hien
authors.initials: MH
authors.lastname: Hoang
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Jia
authors.forename: Hee-jin
authors.initials: HJ
authors.lastname: Jun
authors.forename: Ji-Hae
authors.initials: JH
authors.lastname: Lee
authors.forename: Dong-Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Bang-Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: Woo-Jin
authors.initials: WJ
authors.lastname: Kim
authors.forename: Hak-Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D017930:Genes, Reporter; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009928:Organ Specificity; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000235:genetics; D020349:Surface Plasmon Resonance; D015533:Transcriptional Activation / Q000187:drug effects; D034401:Ulmaceae / Q000737:chemistry
chemical_list: D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; C575103:ethyl 2,4,6-trihydroxybenzoate; D005707:Gallic Acid; D002784:Cholesterol