title: Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, improves hepatic microcirculatory patency and oxygen availability in a high-fat-diet-induced fatty liver in mice.
abstract: Nonalcoholic fatty liver disease (NAFLD) is a common disease of chronic liver diseases. Peroxisome proliferator-activated receptor alpha (PPARalpha) has been implicated to play important roles in the development of the disease. Beyond its effects on lipid metabolisms, PPARalpha 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 PPARalpha 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 PPARalpha activated by fenofibrate on the regulation of both lipid metabolisms and microvascular environments of oxygen metabolism in HFD-induced fatty liver.
authors.affiliation: Department of Biochemistry and Integrative Medical Biology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kondo
authors.forename: Tadao
authors.initials: T
authors.lastname: Sugioka
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tsukada
authors.forename: Michiyoshi
authors.initials: M
authors.lastname: Aizawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takizawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
authors.forename: Masaya
authors.initials: M
authors.lastname: Morimoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Goda
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology; D005234:Fatty Liver / Q000139:chemically induced / Q000188:drug therapy*; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism*; D047493:PPAR alpha / Q000819:agonists*; D014654:Vascular Patency / Q000187:drug effects*
chemical_list: D004041:Dietary Fats; D047493:PPAR alpha; D010100:Oxygen; D011345:Fenofibrate