Dual action of isoprenols from herbal medicines on both PPARgamma and PPARalpha in 3T3-L1 adipocytes and HepG2 hepatocytes

Nobuyuki Takahashi; Teruo Kawada; Tsuyoshi Goto; Takayuki Yamamoto; Aki Taimatsu; Naoko Matsui; Kazuhiro Kimura; Masayuki Saito; Masashi Hosokawa; Kazuo Miyashita; Tohru Fushiki

doi:10.1016/s0014-5793(02)02390-6

Dual action of isoprenols from herbal medicines on both PPARgamma and PPARalpha in 3T3-L1 adipocytes and HepG2 hepatocytes

FEBS Lett. 2002 Mar 13;514(2-3):315-22. doi: 10.1016/s0014-5793(02)02390-6.

Authors

Nobuyuki Takahashi¹, Teruo Kawada, Tsuyoshi Goto, Takayuki Yamamoto, Aki Taimatsu, Naoko Matsui, Kazuhiro Kimura, Masayuki Saito, Masashi Hosokawa, Kazuo Miyashita, Tohru Fushiki

Affiliation

¹ Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.

PMID: 11943173
DOI: 10.1016/s0014-5793(02)02390-6

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Adipocytes / cytology
Adipocytes / drug effects
Adipocytes / metabolism*
Animals
CREB-Binding Protein
Carotenoids / chemistry
Carotenoids / pharmacology
Cell Line
Diterpenes / chemistry
Diterpenes / pharmacology
Dose-Response Relationship, Drug
Farnesol / chemistry
Farnesol / pharmacology
Genes, Reporter
Hepatocytes / cytology
Hepatocytes / drug effects
Hepatocytes / metabolism*
Humans
Ligands
Mice
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Oleic Acid / pharmacology
Plant Preparations* / chemistry
Polymerase Chain Reaction
Receptors, Cytoplasmic and Nuclear / drug effects
Receptors, Cytoplasmic and Nuclear / metabolism*
Terpenes / chemistry
Terpenes / pharmacology*
Trans-Activators / genetics
Trans-Activators / metabolism
Transcription Factors / drug effects
Transcription Factors / metabolism*
Transfection
Up-Regulation / drug effects

Substances

Diterpenes
Ligands
Nuclear Proteins
Plant Preparations
Receptors, Cytoplasmic and Nuclear
Terpenes
Trans-Activators
Transcription Factors
Oleic Acid
Carotenoids
Farnesol
geranylgeraniol
CREB-Binding Protein
CREBBP protein, human
Crebbp protein, mouse