The regulatory role of fatty acid metabolism in development of NASH

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15188
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: University of Tsukuba
• Principal Investigator: MIZOKAMI Yuji 筑波大学, 医学医療系, 准教授 (70268556)
• Co-Investigator(Kenkyū-buntansha): 蕨 栄治 筑波大学, 医学医療系, 講師 (70396612) ; 岡田 浩介 筑波大学, 附属病院, 病院講師 (80757526) ; 正田 純一 筑波大学, 医学医療系, 教授 (90241827)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 非アルコール性脂肪性肝炎 / p62 / 脂肪酸代謝

Outline of Final Research Achievements

We generated p62 knockout (p62-KO) mice and demonstrated that these mice developed to simple steatosis in the livers by the obesity induced by hyperphagia. Moreover, we found that p62-KO mice developed to steatohepatitis with severe steatosis, inflammatory and fibrosis in the livers induced by 60% high fat diet (HFD). We supposed the mechanism for the development of steatohepatitis in p62-KO mice fed HFD that p62 influenced free fatty acid (FFA) metabolism and resulted in unbalance between FFA and fatty acyl-CoA in the hepatocytes. Futhermore, deletion of p62 may be related the failure of “lipophagy”, important system for lipid and FFA metabolism. We plan to compare between p62-KO and p62 gene rescued mice in hepatocytes, and p62 knockout hepatocytes and WT hepatocytes. And we will research the detail of mechanism for development of NASH and the contribution of p62 focused on the FA metabolism and lipophagy in the near future.

Free Research Field

消化器内科