The role of spleen-derived IL-10 and portal GLP-1 levels in the prevention of obesity-induced dementia

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K01721
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Oita University
• Principal Investigator: Gotoh Koro 大分大学, 医学部, 助教 (10457624)
• Co-Investigator(Kenkyū-buntansha): 正木 孝幸 大分大学, 医学部, 講師 (00423715) ; 植田 聡 大分大学, 医学部, 助教 (00624511) ; 柴田 洋孝 大分大学, 医学部, 教授 (20245484) ; 加隈 哲也 大分大学, 保健管理センター, 准教授 (80343359)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 肥満 / GLP-1 / BDNF / アルツハイマー型認知症

Outline of Final Research Achievements

Obesity induces systemic low-grade chronic inflammation. Dementia is deeply related with amyloid deposition although the mechanism is uncertain. BDNF is an important factor to prevent neuronal death which occurs in Alzheimer's disease. The aim of this study is to clarify that the elevation of GLP-1 secretion improves obesity-induced decrease of BDNF expression in the brain. Splenectomy (SPX) promotes obesity-induced decrease of GLP-1 expression and increase of DPP-4 activity in small intestine. Chronic IL-10 treatment attenuated these SPX-induced alterations. Moreover, SPX also worsened obesity-induced reduction of BDNF expression in the brain, and IL-10 treatment recovered this expression. There was no difference among all groups in amyloid deposits in the brain. In addition, we clarified that the administration of a DPP-4 inhibitor elevated BDNF expression in the brain. Thus, the GLP-1 might induce BDNF expression in the brain and be effective to prevent the development of dementia.

Free Research Field

神経内分泌学