Effect of RAGE on feeding and metabolism by the inflammation regulation mechanism of the hypothalamus

Research Project

Project/Area Number	18K16248
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 54040:Metabolism and endocrinology-related
Research Institution	Hyogo Medical University
Principal Investigator	Konishi Kosuke 兵庫医科大学, 医学部, 講師 (90532367)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000) Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords	RAGE / esRAGE / 脳内炎症 / 肥満 / 視床下部炎症 / sRAGE / TNF-α / ADAM10 / MMP9 / AGEs / 視床下部
Outline of Final Research Achievements	RAGE(receptor for advanced glycation end-products, AGE) acts as a mediator of inflammation and has been reported to be associated with vascular endothelial inflammation, diabetes, obesity and intracerebral inflammation.We reported the results of research on RAGE and soluble RAGE (sRAGE) and inflammatory signal control mechanism in vascular endothelial cells.It supports the hypothesis that "RAGE and its shedding regulate inflammation of the hypothalamus and are involved in the development of obesity and diabetes through feeding behavior and basal metabolic balance."
Academic Significance and Societal Importance of the Research Achievements	終末糖化産物 (advanced glycation end-products, AGE)受容体であるRAGE(receptor for AGE)は炎症のメディエーターとして働き、血管内皮炎症、糖尿病、肥満の病態に関与する。今回、我々が報告した、血管内皮細胞におけるRAGEおよび可溶性RAGE(sRAGE)と炎症シグナルの制御機構の研究成果を踏まえると、RAGEおよびその切断機序が脳内炎症の調節を介して、摂食行動、基礎代謝バランスの撹乱に関与し、肥満・糖尿病の発症に関与する可能性が示唆される。今回の成果は、慢性疾患における脳内炎症のメカニズムの解明とその予防戦略の構築に寄与できると考える。