| Project/Area Number |
24590995
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Juntendo University |
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Principal Investigator |
KON Kazuyoshi 順天堂大学, 医学部, 准教授 (30398672)
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| 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)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| 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 / NAFLD / 肝細胞がん / カルニチン / 酸化ストレス / 肝細胞癌 / 肝線維化 / 脂肪肝 / 非アルコール脂肪肝炎 / 高脂肪食 / 食事療法 / 運動療法 / 遊離脂肪酸 |
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| 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.
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