Auraptene, a citrus fruit compound, regulates gene expression as a PPARalpha 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 (PPARalpha) activation. To examine effects of auraptene on the PPARalpha activation in hepatocytes, PPAR ligand assay system was developed using HepG2 hepatocytes, in which the endogenous PPARalpha expression level is very low. In the PPAR ligand assay, the addition of auraptene showed significant effects on the transactivation of GAL4/PPARalpha 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 PPARalpha-expressing HepG2 hepatocytes. The regulation of gene expression was dependent on PPARalpha 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 PPARalpha-expressing HepG2 hepatocytes. These results indicate that auraptene acts as a PPARalpha agonist in hepatocytes and that auraptene may improve lipid abnormality through PPARalpha activation in the liver.
Takahashi
Nobuyuki
N
Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
Kang
Min-Sook
MS
Kuroyanagi
Kayo
K
Goto
Tsuyoshi
T
Hirai
Shizuka
S
Ohyama
Kana
K
Lee
Joo-Young
JY
Yu
Rina
R
Yano
Masamichi
M
Sasaki
Takao
T
Murakami
Shigeru
S
Kawada
Teruo
T
D045744:Cell Line, Tumor; D003374:Coumarins / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D047493:PPAR alpha / Q000819:agonists* / Q000096:biosynthesis
D003374:Coumarins; D005227:Fatty Acids; D047493:PPAR alpha; C105832:aurapten