Dual action of isoprenols from herbal medicines on both PPARγ and PPARα in 3T3‐L1 adipocytes and HepG2 hepatocytes

FEBS Letters

Miyashita, Kazuo²  Taimatsu, Aki¹  Saito, Masayuki²  Goto, Tsuyoshi¹  Hosokawa, Masashi²  Kawada, Teruo¹  Yamamoto, Takayuki¹  Kimura, Kazuhiro²  Fushiki, Tohru¹  Matsui, Naoko¹  Takahashi, Nobuyuki¹ 

[1] Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan;Project for Obesity and Lipid Metabolism Regulation, Bio-oriented Research Advancement Institute (BRAIN), Tokyo 105-0001, Japan

关键词: Lipid metabolism;    Insulin resistance;    Obesity;    Isoprenoid;    Thiazolidinedione;    Fibrate;    HMG-CoA;    3-hydroxy-3-methylglutaryl-coenzyme A;    PPAR;    peroxisome proliferator-activated receptor;    PPRE;    PPAR-response element;    CBP;    CREB-binding protein;    CREB;    cAMP-response-element-binding protein;    aP2;    adipocyte fatty acid-binding protein;    LPL;    lipoprotein lipase;    CPT1A;    carnitine palmitoyltransferase 1 liver;    ACS;    acyl-CoA synthetase;    ECH;    enoyl-CoA hydratase;    GAPDH;    glyceraldehyde-3-phosphate dehydrogenase;   

DOI  :  10.1016/S0014-5793(02)02390-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 PPARγ but also PPARα as determined using the chimera assay system. These compounds also activated full-length human PPARγ and PPARα in CV1 cells. Moreover, these isoprenols upregulated the expression of some lipid metabolic target genes of PPARγ and PPARα in 3T3-L1 adipocytes and HepG2 hepatocytes, respectively. These results suggest that herbal medicines containing isoprenols with dual action on both PPARγ and PPARα can be of interest for the amelioration of lipid metabolic disorders associated with diabetes.

【 授权许可】

Unknown