| Project/Area Number |
24590996
|
|---|
| 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 |
IKEJIMA Kenichi 順天堂大学, 医学(系)研究科(研究院), 准教授 (20317382)
|
|---|
| 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)
|
|---|
| 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)
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| 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)
|
|---|
| 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 |
|---|
| 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.
|
