title: Dual action of isoprenols from herbal medicines on both PPARgamma and PPARalpha in 3T3-L1 adipocytes and HepG2 hepatocytes.
abstract: Several herbal medicines improve hyperlipidemia, diabetes and cardiovascular diseases. However, the molecular mechanism underlying this improvement has not yet been clarified. In this study, we found that several isoprenols, common components of herbal plants, activate human peroxisome proliferator-activated receptors (PPARs) as determined using the novel GAL4 ligand-binding domain chimera assay system with coactivator coexpression. Farnesol and geranylgeraniol that are typical isoprenols in herbs and fruits activated not only PPARgamma but also PPARalpha as determined using the chimera assay system. These compounds also activated full-length human PPARgamma and PPARalpha in CV1 cells. Moreover, these isoprenols upregulated the expression of some lipid metabolic target genes of PPARgamma and PPARalpha in 3T3-L1 adipocytes and HepG2 hepatocytes, respectively. These results suggest that herbal medicines containing isoprenols with dual action on both PPARgamma and PPARalpha can be of interest for the amelioration of lipid metabolic disorders associated with diabetes.
authors.affiliation: Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Aki
authors.initials: A
authors.lastname: Taimatsu
authors.forename: Naoko
authors.initials: N
authors.lastname: Matsui
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saito
authors.forename: Masashi
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Miyashita
authors.forename: Tohru
authors.initials: T
authors.lastname: Fushiki
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D050882:CREB-Binding Protein; D002338:Carotenoids / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005204:Farnesol / Q000737:chemistry / Q000494:pharmacology; D017930:Genes, Reporter; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology; D028321:Plant Preparations / Q000737:chemistry; D016133:Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004224:Diterpenes; D008024:Ligands; D009687:Nuclear Proteins; D028321:Plant Preparations; D018160:Receptors, Cytoplasmic and Nuclear; D013729:Terpenes; D015534:Trans-Activators; D014157:Transcription Factors; D019301:Oleic Acid; D002338:Carotenoids; D005204:Farnesol; C017338:geranylgeraniol; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C494364:Crebbp protein, mouse