Development for the prevention of obesity and diabetes by regulation of brown adipose tissue volume using tetrahydrobiopterin

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08903
• 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: Kyoto University
• Principal Investigator: Fujita Yoshihito 京都大学, 医学研究科, 講師 (50547809)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 糖尿病 / 肥満症 / 褐色脂肪組織

Outline of Final Research Achievements

The purpose of this study was to elucidate the mechanisms by which neonatal BH4 affects postnatal metabolism via BAT and to develop treatments for diabetes and obesity. BAT from BH4-deficient mice at birth and control mice were collected to explore the factors involved. Metabolome analysis and RNA sequencing analysis enabled us to discriminate between the two groups, and we found factors that contributed to the differences. Furthermore, when BH4 was administered intraplacenta to BH4-deficient mice from the prenatal period, BH4 function at birth was restored. Characterization of the BAT of mice born after this intraplacental BAT administration showed that they had genetic and metabolic characteristics similar to the BAT of control mice.

Free Research Field

糖尿病、肥満症

Academic Significance and Societal Importance of the Research Achievements

BATは熱産生によりエネルギー代謝を促進させる臓器であり、新たな肥満症・糖尿病の治療標的として注目されている。BH4はnitric oxideやカテコラミン合成酵素の補酵素として作用しBATを活性化させる物質である。申請者らはこのBH4を妊娠後期の母体マウスに投与したところ新生児マウスのBAT重量が増加することを見出した。さらに、成長後の糖尿病・肥満症の発症を予防できる可能性を示す所見を見出した。これらの機能に関与する因子を見出しており、新たな糖尿病・肥満症の発症予防、治療の標的の開発につながる成果が得られた。