The involvement of oxidative stress in high fat diet-induced nonalcoholic steatohepatitis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18993
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Matsumoto Misaki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80533926)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 非アルコール性脂肪性肝炎 / 酸化ストレス / 肝類洞 / 一酸化窒素

Outline of Final Research Achievements

Nonalcoholic steatohepatitis (NASH) is strongly associated with obesity and metabolic syndrome. Oxidative stress is known to play a critical role in the development of NASH. In this study, we demonstrated that NOX1/NADPH oxidase is involved in the high fat diet (HFD)-induced liver injury. The mRNA expression of NOX1, but not of NOX2 or NOX4 was significantly elevated after 8 weeks of HFD. The expression of NOX1 mRNA was much higher in the fractions of liver sinusoidal endothelial cells (LSECs) than in those of hepatocytes. In primary cultured LSECs, palmitic acid, a saturated free fatty acid, significantly up-regulated the level of NOX1 mRNA. The increase in NOX1 induced the nitrotyrosine adduct formation in hepatic sinusoids, the in vitro reduction of nitric oxide and the in vitro contraction of hepatic stellate cells. Accordingly, oxidative stress derived from NOX1 in LSECs may accelerate hepatocellular injury by impairment of hepatic microcirculation in NASH.

Free Research Field

病態分子薬理学