Elucidation of the relationship between obesity and type 2 diabetes in achondroplasia

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K23996
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0904:Internal medicine of the bio-information integration and related fields
• Research Institution: Osaka University
• Principal Investigator: FUJIWARA MAKOTO 大阪大学, 歯学研究科, 助教 (50625697)
• Project Period (FY): 2019-08-30 – 2022-03-31
• Keywords: 軟骨無形成症 / 2型糖尿病 / 肥満

Outline of Final Research Achievements

Achondroplasia is a congenital bone disease. Although the patients frequently show obesity with a characteristic fat distribution, it is known that the morbidity of type 2 diabetes mellitus is low. In this study, we aimed to elucidate the mechanism of glucose metabolism in this disease. We induced iPS cells from achondroplasia patients and healthy subjects respectively, differentiated them into mesenchymal stem cells, and compared and examined their ability to differentiate into adipocytes. As a result, no clear difference was shown in the adipogenesis between the patients and healthy control, suggesting an integrated mechanism of fat differentiation and glucose tolerance at the biological level. Therefore, we have established an experimental system using achondroplasia model mice, which is necessary for in vivo analysis.

Free Research Field

医学（小児骨系統疾患、内分泌疾患）

Academic Significance and Societal Importance of the Research Achievements

2型糖尿病は本邦で社会・生活環境の変化に伴い罹患者数が増加しており、肥満はその重要な因子の一つである。軟骨無形成症では特異的な肥満と、2型糖尿病となりにくい性質が知られ、何らかの特有の糖・脂肪・エネルギーの代謝状態を発現している可能性があるが、その機序は不明である。本研究では、軟骨無形成症の病態の影響は、細胞レベルの脂肪分化において明らかでないことが示され、生体レベルでの統合的な調節が行われている可能性が示唆された。本研究で全身の組織で病態を再現する軟骨無形成症のモデルマウスを用いる実験系を確立したことは、今後この本疾患に特徴的な脂肪分化・糖代謝の解明に向けて大きな意義があると考えられる。