Phytol directly activates peroxisome proliferator-activated receptor alpha (PPARalpha) and regulates gene expression involved in lipid metabolism in PPARalpha-expressing HepG2 hepatocytes

Biochem Biophys Res Commun. 2005 Nov 18;337(2):440-5. doi: 10.1016/j.bbrc.2005.09.077. Epub 2005 Sep 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Clofibric Acid / pharmacology
  • Gene Expression Regulation / drug effects*
  • Haplorhini
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Humans
  • Lipid Metabolism / drug effects*
  • Liver / metabolism
  • Luciferases / metabolism
  • PPAR alpha / drug effects
  • PPAR alpha / metabolism*
  • Phytanic Acid / metabolism
  • Phytol / pharmacology*
  • Transcription Factors / genetics
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • PPAR alpha
  • Transcription Factors
  • Phytanic Acid
  • Phytol
  • Clofibric Acid
  • Luciferases