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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Title of host publicationOxygen Transport to Tissue XXXI
EditorsEiji Takahashi, Duane Bruley
Pages77-82
Number of pages6
DOIs
Publication statusPublished - 2010 Dec 1

Publication series

NameAdvances in Experimental Medicine and Biology
Volume662
ISSN (Print)0065-2598

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kondo, K., Sugioka, T., Tsukada, K., Aizawa, M., Takizawa, M., Shimizu, K., Morimoto, M., Suematsu, M., & Goda, N. (2010). 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. In E. Takahashi, & D. Bruley (Eds.), Oxygen Transport to Tissue XXXI (pp. 77-82). (Advances in Experimental Medicine and Biology; Vol. 662). https://doi.org/10.1007/978-1-4419-1241-1_10