Elucidation of metabolic rhythm regulation by orexin agonist

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K11014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: University of Tsukuba
• Principal Investigator: Fukusumi Shoji 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (10750002)
• Co-Investigator(Kenkyū-buntansha): 櫻井 勝康 筑波大学, 国際統合睡眠医科学研究機構, 助教 (70507920) ; 斉藤 毅 筑波大学, 国際統合睡眠医科学研究機構, 助教 (80609933) ; 入鹿山 容子 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (90312834)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 睡眠 / オレキシン

Outline of Final Research Achievements

We demonstrate the potential metabolic effects of a non-peptide OX2R selective agonist, YNT-185 by using high-fat fed mice. C57BL/6J mice was single-housed under high-fat diet for one week and daily intraperitoneal administration of YNT-185 or vehicle was performed during light period (ZT6). As a result, the body weight gain of the YNT-185-treated group was attenuated along with the decrease in the food intake compared to the control group. Moreover, the weights of epididymal adipose tissues in the YNT-185-treated group were significantly reduced compared to the control group. It is suggested that the YNT-185 attenuates diet-induced body weight gain by reducing the accumulation of peripheral fat at least via suppression of food intake. The pharmacological effects may depend on the clock time of the administration. To validate the effectiveness on metabolic abnormalities, the pharmacological mechanisms of YNT-185 against body weight gain need to be elucidated by further investigation.

Free Research Field

創薬

Academic Significance and Societal Importance of the Research Achievements

メタボリックシンドローム、いわゆる肥満は多くの場合、合併症により健康寿命を短くし、QOLの低下を招くだけでなく、医療費を圧迫するなど大きな社会問題となっている。一方、代謝改善薬としてオレキシン系を標的にしたものは現在のところ存在しない。今回の結果から、オレキシン2型受容体作動薬は将来的に全く新しい機序の代謝改善薬として有望である。また、既存の治療法とは作用部位が異なるため、既知の治療法との併用により相加・相乗効果が期待できる。