Affiliations: Laboratory of Molecular Function of Food, Division of
Food Science and Biotechnology, Graduate School of Agriculture, Kyoto
University, Uji, Kyoto, Japan | Department of Food Science and Nutrition, University
of Ulsan, Ulsan, South Korea | Department of Citriculture, National Institute of
Fruit Tree Sciences, Ministry of Agriculture, Forestry and Fisheries, Shimizu,
Shizuoka, Japan | ARKRAY Inc., Kyoto, Japan | Taisho Pharmaceutical Co. Ltd., Toshima-ku, Tokyo,
Japan
Note: [] Address for correspondence: Teruo Kawada, Laboratory of
Molecular Function of Food, Division of Food Science and Biotechnology,
Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
Fax: +81 774 38 3752; E-mail: fat@kais.kyoto-u.ac.jp
Abstract: 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-α
(PPARα) activation. To examine effects of auraptene on
the PPARα activation in hepatocytes, PPAR ligand assay
system was developed using HepG2 hepatocytes, in which the endogenous
PPARα expression level is very low. In the PPAR ligand
assay, the addition of auraptene showed significant effects on the
transactivation of GAL4/PPARα 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
PPARα-expressing HepG2 hepatocytes. The regulation of
gene expression was dependent on PPARα 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 PPARα-expressing HepG2 hepatocytes. These
results indicate that auraptene acts as a PPARα agonist
in hepatocytes and that auraptene may improve lipid abnormality through
PPARα activation in the liver.
