Molecular nutritional signaling via MCFA and ketone body receptors

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19731
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: Kimura Ikuo 東京農工大学, (連合)農学研究科(研究院), 教授 (80433689)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 中鎖脂肪酸 / ケトン体 / GPR84 / GPR109A / GPR41 / GPR43

Outline of Final Research Achievements

Ketone bodies, mainly β-hydroxybutyrate and acetoacetate, are important alternative energy sources in a state of energy deficit or metabolic crisis. The consumption of ketogenic diets, such as low-carbohydrate and medium-chain triglyceride diets, and time-restricted feeding lead to ketogenesis, which influences longevity and health. β-Hydroxybutyrate also acts as a signaling molecule via GPR109A and GPR41; however, to date, the specific G protein-coupled receptors responsible for acetoacetate and its physiological functions remain unknown. In this study, we demonstrated that acetoacetate acts as an endogenous agonist of GPR43 by ligand screening in a heterologous expression system, and that it, rather than short-chain fatty acids, maintains energy homeostasis via GPR43-mediated lipid metabolism under ketogenic conditions.

Free Research Field

内分泌代謝学、食品科学、栄養学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、中鎖脂肪酸やその生体代謝物であるケトン体が、エネルギー源としてではなくシグナル伝達物質として、細胞膜上受容体を介して生理機能調節、特にエネルギー代謝制御に寄与する新たなメカニズムの一端を明らかにした。このようなケトン体とその受容体を介した分子栄養メカニズムの解明は、栄養管理による先制医療や予防医学、更にはケトン体受容体を標的とした代謝性疾患治療薬の開発に向けて、今後、本成果の応用が期待される。