The impact of hepatocyte apoptosis and autophagy in the process of livercarcinogenesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 26253047
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: Takehara Tetsuo 大阪大学, 医学系研究科, 教授 (70335355)
• Co-Investigator(Kenkyū-buntansha): 巽 智秀 大阪大学, 医学系研究科, 講師 (20397699) ; 疋田 隼人 大阪大学, 医学系研究科, 助教 (20623044)
• Research Collaborator: TANAKA Satoshi 大阪大学, 大学院医学系研究科 ; SAKANE Sadatsugu 大阪大学, 大学院医学系研究科
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 脂肪肝 / 肝細胞 / オートファジー / アポトーシス / Rubicon

Outline of Final Research Achievements

We investigated autophagic change in the liver and the effect on liver apoptosis and lipid accumulation in NAFLD model. In liver cell lines, palmitic acid (PA) treatment suppressed autophagy with increase of Rubicon. Rubicon blockade attenuated autophagy impairment and reduced palmitate-induced apoptosis and lipid accumulation. The Rubicon increase by PA was caused by suppression of Rubicon degradation. Rubicon was also up-regulated in association with autophagy impairment in livers of mice fed a high-fat diet (HFD). Hepatocyte-specific Rubicon knockout mice showed amelioration of liver steatosis and injury as well as attenuation of autophagy impairment for four months HFD feeding.　In humans, liver tissues obtained from patients with NAFLD expressed significantly higher levels of Rubicon than those without steatosis. Rubicon might be a new therapeutic target for NAFLD progression.

Free Research Field

消化器内科学