Phytol directly activates peroxisome proliferator-activated receptor alpha (PPARalpha) and regulates gene expression involved in lipid metabolism in PPARalpha-expressing HepG2 hepatocytes.
The peroxisome proliferator-activated receptor (PPAR) is one of the indispensable transcription factors for regulating lipid metabolism in various tissues. In our screening for natural compounds that activate PPAR using luciferase assays, a branched-carbon-chain alcohol (a component of chlorophylls), phytol, has been identified as a PPARalpha-specific activator. Phytol induced the increase in PPARalpha-dependent luciferase activity and the degree of in vitro binding of a coactivator, SRC-1, to GST-PPARalpha. Moreover, the addition of phytol upregulated the expression of PPARalpha-target genes at both mRNA and protein levels in PPARalpha-expressing HepG2 hepatocytes. These findings indicate that phytol is functional as a PPARalpha ligand and that it stimulates the expression of PPARalpha-target genes in intact cells. Because PPARalpha activation enhances circulating lipid clearance, phytol may be important in managing abnormalities in lipid metabolism.
Goto
Tsuyoshi
T
Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Japan.
Takahashi
Nobuyuki
N
Kato
Sota
S
Egawa
Kahori
K
Ebisu
Shogo
S
Moriyama
Tatsuya
T
Fushiki
Tohru
T
Kawada
Teruo
T
D000818:Animals; D001483:Base Sequence; D002995:Clofibric Acid / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D000882:Haplorhini; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D047493:PPAR alpha / Q000187:drug effects / Q000378:metabolism*; D010831:Phytanic Acid / Q000378:metabolism; D010836:Phytol / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D047493:PPAR alpha; D014157:Transcription Factors; D010831:Phytanic Acid; D010836:Phytol; D002995:Clofibric Acid; D008156:Luciferases