Development of overeating-induced obese mouse assuming human life style-related diseases and investigation of pathophysiological factors associated with NASH

2015 Fiscal Year Final Research Report

• Project/Area Number: 25282212
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: University of Tsukuba
• Principal Investigator: Mizogami Yuji 筑波大学, 医学医療系, 准教授 (70268556)
• Co-Investigator(Kenkyū-buntansha): YANAGAWA Toru 筑波大学, 医学医療系, 准教授 (10312852) ; UTSUNOMIYA Hirotoshi 和歌山県立医科大学, 共同利用施設, 准教授 (60264876) ; ISOBE Tomonori 筑波大学, 医学医療系, 准教授 (70383643) ; WARABI Eiji 筑波大学, 医学医療系, 講師 (70396612) ; SHODA Junichi 筑波大学, 医学医療系, 教授 (90241827)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 肥満 / 非アルコール性脂肪性肝炎 / 遺伝子改変マウス / リポ多糖 / Kupffer細胞

Outline of Final Research Achievements

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that develops from simple steatosis to liver cirrhosis and hepatocellular carcinoma. Effective prevention and treatment methods are strongly desired. We generated double knockout (DKO) mice without Sqstm1 and Nrf2 genes. In DKO mice, a number of biological molecules from the intestine and adipose tissue in addition to liver may play central roles in the onset of NASH. The serum LPS levels were significantly higher in DKO mice than that 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. The overload of serum LPS 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.

Free Research Field

生活習慣病