Fenofibrate, a peroxisome proliferator-activated receptor a agonist, improves hepatic microcirculatory patency and oxygen availability in a high-fat-diet-induced fatty liver in mice

Kazunari Kondo, Tadao Sugioka, Kosuke Tsukada, Michiyoshi Aizawa, Masayuki Takizawa, Kenji Shimizu, Masaya Morimoto, Makoto Suematsu, Nobuhito Goda*

*この研究の対応する著者

研究成果: Conference contribution

26 被引用数 (Scopus)

抄録

Nonalcoholic fatty liver disease (NAFLD) is a common disease of chronic liver diseases. Peroxisome proliferator-activated receptor a (PPARa) has been implicated to play important roles in the development of the disease. Beyond its effects on lipidmetabolisms, PPARa activation in the vascular system has emerged as an attractive therapeutic potential for NAFLD, although its actions in the microcirculatory system are not fully understood. In this study, we investigated the effects of fenofibrate, a PPARa synthetic agonist, on hepatic microcirculation in a high-fat diet (HFD)-induced fatty liver in mice. In vivo imaging analysis revealed the adverse effects of HFDon hepatic vasculature with narrowing of hepatic sinusoids and hepatic microcirculatory perfusion. Oxygen tension was significantly decreased in portal venules, while NADH autofluorescence in hepatocytes was greatly elevated. Fenofibrate treatment remarkably improved microvascular patency, tissue oxygenation and redox states in the affected liver. These results suggest beneficial roles of PPARa activated by fenofibrate on the regulation of both lipid metabolisms and microvascular environments of oxygen metabolism in HFD-induced fatty liver.

本文言語English
ホスト出版物のタイトルOxygen Transport to Tissue XXXI
編集者Eiji Takahashi, Duane Bruley
ページ77-82
ページ数6
DOI
出版ステータスPublished - 2010

出版物シリーズ

名前Advances in Experimental Medicine and Biology
662
ISSN(印刷版)0065-2598

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

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