Mechanism of beneficial effect of a compound identified by genomic-based drug discovery on metabolic disorders

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08864
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: University of the Ryukyus
• Principal Investigator: Imamura Minako 琉球大学, 医学(系)研究科(研究院), 准教授 (00596124)
• Co-Investigator(Kenkyū-buntansha): 前田 士郎 琉球大学, 医学(系)研究科(研究院), 教授 (50314159) ; 松波 雅俊 琉球大学, 医学(系)研究科(研究院), 助教 (60632635)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ゲノム創薬 / 多因子疾患 / 遺伝要因

Outline of Final Research Achievements

Genome-wide association studies (GWAS) have identified more than 500 genetic
loci associated with susceptibility for type 2 diabetes (T2D). We have previously proposed severalnew potential pharmacological targets for T2D treatments using systematic　bioinformatics approach integrating the findings of GWAS for T2D, and biological or pharmacological information from various databases. KIF11 is one of the potential therapeutic targets identified by the in silico pipeline. In this study, we examined the beneficial effect against metabolic disorders of a KIF11 inhibitor, using diet-induced obesity model mice, and further investigated the detailed mechanism by in vitro study. The study has identified that a KIF11 inhibitor suppressed body weight gain in diet-induced obesity model mice, which mechanism could be explained by the inhibition of adipocyte differentiation by a KIF11 inhibitor.

Free Research Field

生活習慣病の遺伝要因解明とその臨床応用

Academic Significance and Societal Importance of the Research Achievements

近年のゲノム解析技術の進歩により、これまでに多くの生活習慣病の疾患感受性遺伝子領域が同定されてきた。しかし、これらの成果の臨床への還元は十分に達成されていない。本研究では新しいゲノム創薬手法により同定された新規候補治療薬の食事性肥満に対する予防効果をin vivo 実験系で検証し、さらに培養細胞を用いてその機序の一部を明らかにした。本研究の成果は新規の肥満および２型糖尿病の予防・治療法開発に有用な知見であり、さらにゲノム研究成果の効率的な臨床応用に貢献しうることを示すものである。