title: Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-α.
abstract: Peroxisome proliferator-activated receptor-alpha (PPARα) is a nuclear receptor that regulates the expression of genes related to cellular lipid uptake and oxidation. Thus, PPARα agonists may be important in the treatment of hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that catalposide is a novel natural PPARα agonist, identified from reporter gene assay-based activity screening with approximately 900 natural plant and seaweed extracts. Results of time-resolved fluorescence resonance energy transfer analyses suggested that the compound interacted directly with the ligand-binding domain of PPARα. Cultured hepatocytes stimulated with catalposide exhibited significantly reduced cellular triglyceride concentrations, by 21%, while cellular uptake of fatty acids was increased, by 70% (P<0.05). Quantitative PCR analysis revealed that the increase in cellular fatty acid uptake was due to upregulation of fatty acid transporter protein-4 (+19% vs. the control) in cells stimulated with catalposide. Additionally, expression of genes related to fatty acid oxidation and high-density lipoprotein metabolism were upregulated, while that of genes related to fatty acid synthesis were suppressed. In conclusion, catalposide is hypolipidemic by activation of PPARα via a ligand-mediated mechanism that modulates the expression of in lipid metabolism genes in hepatocytes.
authors.affiliation: Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Lee
authors.forename: Hee-jin
authors.initials: HJ
authors.lastname: Jun
authors.forename: Minh-Hien
authors.initials: MH
authors.lastname: Hoang
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Jia
authors.forename: Xiang Hua
authors.initials: XH
authors.lastname: Han
authors.forename: Dong-Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Hak-Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D005227:Fatty Acids / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D017930:Genes, Reporter / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000378:metabolism*; D008024:Ligands; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000032:analysis; D047493:PPAR alpha / Q000819:agonists*
chemical_list: D005227:Fatty Acids; D005960:Glucosides; D008024:Ligands; D008055:Lipids; D047493:PPAR alpha; C006928:catalposide