Auraptene, a citrus fruit compound, regulates gene expression as a PPAR alpha agonist in HepG2 hepatocytes

Citrus fruit compounds have various activities that improve pathological conditions in many tissues. In this study, we examined the effect of auraptene contained mainly in the peel of citrus on peroxisome proliferator-activated receptor-alpha (PPAR alpha) activation. To examine effects of auraptene on the PPAR alpha activation in hepatocytes, PPAR ligand assay system was developed using HepG2 hepatocytes, in which the endogenous PPAR alpha expression level is very low. In the PPAR ligand assay, the addition of auraptene showed significant effects on the transactivation of GAL4/PPAR alpha chimera proteins in a dose-dependent manner. Actually, treatment with auraptene induced the up-regulation of PPAR target genes, such as acyl-CoA oxidase (ACO), carnitine-palmitoyl transferase 1A (CPT1A) and acyl-CoA synthetase (ACS), in PPAR alpha-expressing HepG2 hepatocytes. The regulation of gene expression was dependent on PPAR alpha because mock-transfected HepG2 hepatocytes showed no regulation. The up-regulation of PPAR target gene expression by auraptene was sufficient to enhance oleic acid uptake into PPAR alpha-expressing HepG2 hepatocytes. These results indicate that auraptene acts as a PPAR alpha agonist in hepatocytes and that auraptene may improve lipid abnormality through PPAR alpha activation in the liver.