Application of Alpha-ketoglutarate for the Treatment of Obesity as an Epigenetic Drug

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16366
• 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: University of Toyama
• Principal Investigator: Okabe Keisuke 富山大学, 学術研究部医学系, 特命講師 (00770702)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: αケトグルタル酸 / 肥満 / 糖尿病 / メタボローム

Outline of Final Research Achievements

In this study, we investigated the effect of α-ketoglutaric acid, a metabolite known to be involved in energy metabolism, on diet-induced obesity. Using mice, we examined the dynamics of metabolites and gene expression in related tissues and organs after α-ketoglutaric acid administration. Based on previous research, it was anticipated that α-ketoglutaric acid would exert inhibitory effects on obesity and associated metabolic disorders. However, in the present study, no anti-obesity effects were observed, nor was there any efficacy in ameliorating glucose metabolism disorders. On the other hand, regarding gene expression in white adipose tissue, administration of α-ketoglutaric acid showed increased some anti-inflammatory markers and the trend to decrease an inflammatory marker.

Free Research Field

代謝内科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により経口的なαケトグルタル酸投与により生体組織内での代謝物濃度に変化を起こしうることが明らかとなった。肥満、糖代謝異常への有効性は認められなかったものの、先行研究においてはαケトグルタル酸の筋肉や寿命に対する好影響も示されていることから、同代謝物の臨床応用の可能性は十分にあると言える。白色脂肪組織での遺伝子発現については、先行研究に矛盾しない結果を示した。これらの点から、本研究は、αケトグルタル酸の臨床応用へ一定の役割を果たしたと言える。