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Fenofibrate, a Peroxisome Proliferator-Activated Receptor α 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
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 662)

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a common disease of chronic liver diseases. Peroxisome proliferator-activated receptor α (PPARα) has been implicated to play important roles in the development of the disease. Beyond its effects on lipid metabolisms, PPARα 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 PPARα 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 HFD on 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 PPARα activated by fenofibrate on the regulation of both lipid metabolisms and microvascular environments of oxygen metabolism in HFD-induced fatty liver.

Keywords

Nonalcoholic Fatty Liver Disease Hepatic Sinusoid Portal Venule Fenofibrate Treatment Hepatic Microcirculation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by Japan Society for the Promotion of Science Grant-in-Aid for Creative Scientific Research 17GS0419 and by CREST, JST.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Kazunari Kondo
    • 1
  • Tadao Sugioka
    • 1
  • Kosuke Tsukada
    • 2
  • Michiyoshi Aizawa
    • 1
  • Masayuki Takizawa
    • 3
  • Kenji Shimizu
    • 3
  • Masaya Morimoto
    • 3
  • Makoto Suematsu
    • 1
  • Nobuhito Goda
    • 4
    • 5
  1. 1.Department of Biochemistry and Integrative Medical BiologyKeio University School of MedicineTokyoJapan
  2. 2.Department of Biochemistry and Integrative Medical BiologySchool of Medicine, Keio UniversityTokyoJapan
  3. 3.ASKA Pharmaceutical Co., Ltd.TokyoJapan
  4. 4.Department of Life Science and Medical Bio-ScienceWaseda University School of Advanced Science and EngineeringTokyoJapan
  5. 5.Core Research for Evolutional Science and TechnologyJapan Science and Technology AgencyKawaguchiJapan

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