• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2015 Fiscal Year Final Research Report

Nrf2 activation inhibits steatohepatitis and liver cancer in overeating-induced obese mice.

Research Project

  • PDF
Project/Area Number 25293278
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field General surgery
Research InstitutionTokyo Women's Medical University

Principal Investigator

Ariizumi Syunnichi  東京女子医科大学, 医学部, 講師 (40277158)

Co-Investigator(Kenkyū-buntansha) NAKAYAMA MASAMITI  東京女子医科大学, 医学部, 講師 (00338980)
YANAGAWA TORU  筑波大学, 医学医療系, 准教授 (10312852)
YAMAMOTO MASAKAZU  東京女子医科大学, 医学部, 教授 (60220498)
UTSUNOMIYA HIROTOSHI  和歌山県立医科大学, 共同利用施設, 准教授 (60264876)
GOTO NAOHIRO  東京海洋大学, 海洋科学技術研究科, 准教授 (60323854)
WARABI EIJI  筑波大学, 医学医療系, 講師 (70396612)
SHODA JUNNICHI  筑波大学, 医学医療系, 教授 (90241827)
Project Period (FY) 2013-04-01 – 2016-03-31
Keywords肥満 / 脂肪性肝炎 / 肝発癌 / 転写因子 / 動物モデル
Outline of Final Research Achievements

We generated double knockout (DKO) mice without Sqstm1 and Nrf2 genes. To confirm a hypothesis for bacteria-induced metabolic liver disease, we focused on the endotoxin produced by Gram-negative bacteria. In DKO mice, severe NASH was developed with the pathological state of steatohepatitis after 30 weeks. The serum endotoxin levels were significantly higher in DKO mice than those in WT mice. Furthermore, the intestinal permeability, and the gram-negative bacteria levels and endotoxin in feces were all increased significantly in DKO mice. DKO mice had a significant decrease in Kupffer cells (KCs)’ phagocytic function compared with WT. The overload of serum endotoxin induced by the modification of intestine microbiota, the increase of intestinal permeability and the impaired clearance of LPS by KCs dysfunction were considered to be important for the progression of NASH in DKO mice. DKO mouse is a novel animal model that develops mature-onset NASH.

Free Research Field

肝臓外科学

URL: 

Published: 2017-05-10  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi