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 PPAR alpha-specific activator. Phytol induced the increase in PPAR alpha-dependent luciferase activity and the degree of in vitro binding of a coactivator, SRC-1, to GST-PPAR alpha. Moreover, the addition of phytol upregulated the expression of PPAR alpha-target genes at both mRNA and protein levels in PPAR alpha-expressing HepG2 hepatocytes. These findings indicate that phytol is functional as a PPAR alpha ligand and that it stimulates the expression of PPAR alpha-target genes in intact cells. Because PPAR alpha activation enhances circulating lipid clearance, phytol may be important in managing abnormalities in lipid metabolism. (c) 2005 Elsevier Inc. All rights reserved.