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Auraptene regulates gene expression involved in lipid metabolism through PPARα activation in diabetic obese mice

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
    2. Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan
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    • These authors contributed equally to this work

  • Mari Senda,

    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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    • These authors contributed equally to this work

  • Shan Lin,

    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
    2. Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan
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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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  • 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
    2. Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, 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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Abstract

Scope: Peroxisome proliferator-activated receptor-α (PPARα) is a key regulator of circulating lipid level. Thus, various food-derived compounds that activate PPARα as agonists have been screened and characterized.

Methods and results: We investigated the effects of auraptene, a citrus-derived compound serving as a PPARα agonist in vitro, on abnormalities in lipid and glucose metabolisms. In high-fat-diet (HFD)-fed KK-Ay diabetic obese mice, auraptene treatment suppressed hyperlipidemia and triglyceride accumulation in the liver and skeletal muscle, and increased the mRNA expression levels of the PPARα target genes involved in fatty acid oxidation in the liver and skeletal muscle. Moreover, the adipocyte size in the auraptene-treated mice was significantly smaller than that in the control HFD-fed mice resulting in the improvement of HFD-induced hyperglycemia and abnormalities in glucose tolerance.

Conclusions: These findings indicate that auraptene activates PPARα also in vivo and its treatment may improve abnormalities in lipid and glucose metabolisms, suggesting that auraptene is a valuable food-derived compound for managing metabolic disorders.

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