A Nuclear Receptor-mediated Choleretic Action of Fibrates is Associated with Enhanced Canalicular Membrane Fluidity and Transporter Activity Mediating Bile Acid-independent Bile Secretion

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著者

    • NISHIOKA Tomoji
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • HYOGO Hideyuki
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • NUMATA Yoshihiro
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • YAMAGUCHI Atsushi
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • KOBUKE Toshiya
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • KOMICHI Daisuke
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • NONAKA Michihiro
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • INOUE Motoki
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • NABESHIMA Yoshitaka
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • OGI Mami
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • IWAMOTO Keiko
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • ISHITOBI Tomokazu
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • AJIMA Takeyoshi
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • CHAYAMA Kazuaki
    • Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
    • TAZUMA Susumu
    • Department of Genaral Medicine, Hiroshima University Hospital

抄録

Fibrates are commonly used lipid-lowering agents that act via PPARα, a member of the nuclear hormone receptor superfamily. The mechanism(s) of fibrate-induced changes in the hepatic canalicular membrane and bile lipids are still unknown. Therefore, the aim of this study was to investigate the influence of fibrates on hepatic lipid metabolism and to assess the hepatocellular cytoprotective effect on hepatocyte canalicular membrane. Male ICR mice were fed standard chow with or without bezafibrate (100 mg/kg) for 6 days. The expression of canalicular membrane transporters (Mdr2 and Mrp2) was evaluated by RT-PCR and Western blotting. Canalicular membrane fluidity was also investigated. Canalicular membrane fluidity was markedly increased by fibrates. The expression of mdr 2 and mrp2 mRNA and protein showed a significant increase in fibrate-treated mice. These results suggested that fibrates improve liver function by enhancing bile secretion. The mechanism of the choleretic action of fibrate therapy might involve the enhancement of bile acid-independent bile secretion, since increased expression of Mdr2 and Mrp2 was found in fibrate-treated animals. These changes were very likely mediated by PPARα, and the increase of canalicular membrane fluidity may have been partly associated with enhancement of this transporter activity.

収録刊行物

  • Journal of atherosclerosis and thrombosis  

    Journal of atherosclerosis and thrombosis 12(4), 211-217, 2005-08-25 

    Japan Atherosclerosis Society

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各種コード

  • NII論文ID(NAID)
    10018365584
  • NII書誌ID(NCID)
    AA11018976
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13403478
  • データ提供元
    CJP書誌  CJP引用  J-STAGE 
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