Innate immune regulation of hepatic metabolism and immuno-nutritional approach for nonalcoholic fatty liver disease
| Project/Area Number |
24590996
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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 |
IKEJIMA Kenichi 順天堂大学, 医学(系)研究科(研究院), 准教授 (20317382)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHINA Shunhei 順天堂大学, 医学部, 准教授 (30338412)
KON Kazuyoshi 順天堂大学, 医学部, 准教授 (30398672)
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| Co-Investigator(Renkei-kenkyūsha) |
SUEMIZU Hiroshi 公益財団法人実験動物中央研究所, バイオメディカル研究部, 部長 (40332209)
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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 |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
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: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 非アルコール性脂肪肝炎（NASH) / メタボリックシンドローム / 自然免疫 / NKT細胞 / 制御性T細胞 / 免疫栄養 / アミノ酸 / グリシン / 非アルコール性脂肪性肝疾患 / 非アルコール性脂肪肝炎 / Th2サイトカイン / 肝発癌 / Kupffer細胞 |
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| Outline of Final Research Achievements |
In this study, we investigated the role of hepatic innate immune responses in the pathogenesis of metabolic syndrome-related nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH). KK-Ay mice, which resemble phenotypes of human metabolic syndrome, showed functional abnormalities of natural killer T cells and regulatory T cells, which result in lower expression of Th2 cytokines, thereby causing phenotypic changes of hepatic macrophages. These alterations in the hepatic innate immune system not only aggravate steatohepatitis, but also play a pivotal role in the development of metabolic dysfunction. Further, we demonstrated that glycine, a non-essential amino acid, modulates hepatic innate immune responses, and ameliorates steatohepatitis in KK-Ay mice. These observations indicate that glycine is a potential immuno-nutrient for prevention and treatment of NASH.
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.2015
Author(s)
Watanabe S, Hashimoto E, Ikejima K, Uto H, Ono M, Sumida Y, Seike M, Takei Y, Takehara T, Tokushige K, Nakajima A, Yoneda M, Saibara T, Shiota G, Sakaida I, Nakamuta M, Mizuta T, Tsubouchi H, Sugano K, Shimosegawa T.
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Journal Title
Hepatol Res.
Volume: 45
Issue: 4
Pages: 363-377
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hyperresponsivity to low-dose endotoxin during progression to nonalcoholic steatohepatitis is regulated by leptin-mediated signaling2012
Author(s)
Imajo K, Fujita K, Yoneda M, Nozaki Y, Ogawa Y, Shinohara Y, Kato S, Mawatari H, Shibata W, Kitani H, Ikejima K, Kirikoshi H, Nakajima N, Saito S, Maeyama S, Watanabe S, Wada K, Nakajima A
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Journal Title
Cell Metab
Volume: 16(1)
Issue: 1
Pages: 44-54
DOI
Related Report
Peer Reviewed
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