2018 Fiscal Year Final Research Report

Development of Novel Evaluation Systems and Treatment Strategies for Obesity/Diabetes-related Cognitive Impairment through Targeting TREM2

Research Project

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Project/Area Number	16K09276
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	General internal medicine(including psychosomatic medicine)
Research Institution	Health Science University (2018) Department of Clinical Research, National Hospital Organization Kyoto Medical Center (2016-2017)
Principal Investigator	Tanaka Masashi 健康科学大学, 健康科学部, 講師 (60381167)
Co-Investigator(Kenkyū-buntansha)	長谷川浩二独立行政法人国立病院機構(京都医療センター臨床研究センター), 展開医療研究部, 研究部長 (50283594) 小谷和彦自治医科大学, 医学部, 教授 (60335510)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	TREM2 / 肥満 / 糖尿病 / 単球 / ミクログリア / 炎症 / 血管合併症 / 認知症
Outline of Final Research Achievements	Genome-wide association studies previously suggested that a cell surface receptor TREM2 is implicated in the development and progression of dementia. The present study provided the first evidence that serum levels of TREM2 may be a novel marker of the diabetes-related cognitive impairment, by the cross-sectional approach using a database of the multicenter prospective observational cohort consisting of patients with obesity and/or type 2 diabetes. We further demonstrated that omega-3 polyunsaturated fatty acids, medications for metabolic diseases, exhibit the novel anti-inflammatory effects through SIRT1 pathways on the activated mouse microglia. These findings could contribute to developing novel predictive markers and effective therapeutic strategies for obesity/diabetes-related dementia.
Free Research Field	代謝免疫学
Academic Significance and Societal Importance of the Research Achievements	これまで糖尿病におけるTREM2の病態意義は不明であったが、本研究にて、血清TREM2は、糖尿病に伴う認知機能低下の新規バイオマーカーとなる可能性が世界に先駆け明らかにされた。さらに、活性化ミクログリアにおいて、生活習慣病薬・オメガ3系不飽和脂肪酸はSIRT1活性化を介した新規抗炎症作用を発揮することを初めて明らかにし、ミクログリアの質的改善・脳内炎症抑制に繋がる新規分子基盤を見出した。これらの成果は、糖尿病に伴う認知機能低下の新規予知指標・治療戦略の開発に貢献できると考えられる。