Innate immune regulation of hepatic metabolism and immuno-nutritional approach for nonalcoholic fatty liver disease

2014 Fiscal Year Final Research Report

• 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
• 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

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.

Free Research Field

消化器病学