The role of ketone body receptor in metabolic homeostasis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K11600
• 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: Kyoto University
• Principal Investigator: Ohue-Kitano Ryuji (大植隆司) 京都大学, 生命科学研究科, 助教 (90791583)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: GPCR / 代謝性疾患 / ケトン体

Outline of Final Research Achievements

Dietary therapy is the most fundamental and practical approach for the treatment of lifestyle diseases such as obesity and metabolic disorders. In recent years, ketogenic diets (low-carbohydrate, high-fat diets) and medium-chain triglyceride diets have been re-evaluated as part of the diversity in dietary therapy. In this study, we investigated a novel molecular mechanism of metabolic regulation based on nutritional signaling mediated by G protein-coupled receptors (GPCRs) that recognize ketone bodies and medium-chain fatty acids involved in ketone body production. As a result, we found potential contributions of medium-chain fatty acids, recognized through medium-chain fatty acid receptors, to the regulation of glucose and energy metabolism and the nutritional immunological control of the liver.

Free Research Field

内分泌・代謝学

Academic Significance and Societal Importance of the Research Achievements

これまで、ケトン体や中鎖脂肪酸によるエネルギー代謝恒常性維持に関して、その詳細な分子作用機序の全容解明には至っていなかった。特に、中鎖脂肪酸は、血中濃度が極めて低値であることから、生体内における生理的意義は不明であった。本研究により、中鎖脂肪酸は、中鎖脂肪酸受容体を介した糖・エネルギー代謝調節への寄与に加えて、代謝性疾患における肝臓での免疫代謝制御とその病態生理学的意義が明らかになった。今後、中鎖脂肪酸受容体を標的とした新規治療薬創出だけでなく、中鎖脂肪酸を含む機能性食品の開発を通じて、代謝性疾患の新たな予防・治療戦略の確立へと繋がることが期待される。