The new strategy of steatohepatitis targeting alteration of epigenetic regulation

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590995
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Juntendo University
• Principal Investigator: KON Kazuyoshi 順天堂大学, 医学部, 准教授 (30398672)
• Co-Investigator(Kenkyū-buntansha): IKEJIMA Kenichi 順天堂大学, 医学部, 准教授 (20317382) ; KAWAKAMI Kyojiro 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 研究員 (90589227)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: エピジェネティクス / NASH / 肝癌 / 化学シャペロン / トランス脂肪酸 / 小胞体ストレス

Outline of Final Research Achievements

To develop a new strategy of steatohepatitis to take the place of dietary and exercise treatment, we investigated the role of epigenetic alterations on the development of steatohepatitis, using mice (in vivo models) and primary-cultured mouse hepatocytes. In particular, we focused the relationship between endoplasmic reticulum (ER) stress and epigenetic changes in hepatocytes.
First, we showed the possibility that the exercise by treadmill increased carnitine pool, followed by improving lipid metabolism and accelerating the effect of low fat diet feeding. Next, we revealed that increase of ER stress in liver induced epigenetic alteration in liver tissue, leading to hepatic fibrosis and carcinogenesis. Finally, we demonstrated that the anti-ER stress treatment with 4-phenylbuthyric acid ameliorated ER stress, followed by improving steatohepatitis in vitro and in vivo.

Free Research Field

肝臓病学