Suppression of alpha-fetoprotein related hepatocellular proliferation and hepatocellular carcinogenesis in nonalcoholic steatohepatitis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590981
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kochi University
• Principal Investigator: SAIBARA Toshiji 高知大学, 教育研究部医療学系, 教授 (60145125)
• Co-Investigator(Kenkyū-buntansha): TODA Katsumi 高知大学, 教育研究部医療学系, 准教授 (40197893) ; ONO Masafumi 高知大学, 教育研究部医療学系, 講師 (70304681)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肝臓学 / NASH / 肝発癌 / エストロゲン / PPAR-α

Outline of Final Research Achievements

Aromatase deficient mice develop hepatic steatosis spontaneously via enhanced lipogenesis with increased glyconeogenesis. PPAR-α expression is decreased in this model and it recovers gradually after exogenous estrogen and/or PPAR-α ligand administration. Impaired PPAR-αexpression is a risk factor for the development of diabetes and hepatic steatosis in the hepatocarcinogenic model using these mice. PPAR-α expression in these mice recovered spontaneously in the liver with chronic inflammation and hepatocellular carcinoma emerged afterward. The frequency of hepatocarcinogenesis in these mice is suppressed when PPAR-α is deficient. These observation suggest that PPAR-α activation mediated process is involved profoundly in the hepatocarcinogenesis in these mice and that estrogen could affect this process to suppress the carcinogenesis efficiently.

Free Research Field

消化器内科