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

Authors

  • Nobuyuki Takahashi,

    1. Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan
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  • Min-Sook Kang,

    1. Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan
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  • Kayo Kuroyanagi,

    1. Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan
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  • Tsuyoshi Goto,

    1. Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan
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  • Shizuka Hirai,

    1. Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan
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  • Kana Ohyama,

    1. Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan
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  • Joo-Young Lee,

    1. Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan
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  • Teruo Kawada,

    Corresponding author
    1. Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan
    • 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
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  • Rina Yu,

    1. Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea
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  • Masamichi Yano,

    1. Department of Citriculture, National Institute of Fruit Tree Sciences, Ministry of Agriculture, Forestry and Fisheries, Shimizu, Shizuoka, Japan
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  • Takao Sasaki,

    1. ARKRAY Inc., Kyoto, Japan
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  • Shigeru Murakami

    1. Taisho Pharmaceutical Co. Ltd., Toshima-ku, Tokyo, Japan
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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.

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