Examination of obesity and insulin resistance for patient cohort and disease-specific iPS cells with achondroplasia

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07877
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Osaka University
• Principal Investigator: Kitaoka Taichi 大阪大学, 医学系研究科, 助教 (20599229)
• Co-Investigator(Kenkyū-buntansha): 木村 武司 大阪大学, 医学部附属病院, 特任助教(常勤) (50774402)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 軟骨無形成症 / 小児肥満 / インスリン抵抗性

Outline of Final Research Achievements

In achondroplasia (ACH), obesity is overestimated by physical evaluation based on the degree of obesity using standard height and weight due to the markedly short stature with limbs shortening. In this study, 32 ACH patients were divided into obese and non-obese groups based on the body fat percentage obtained by the DEXA (dual energy X-ray absorptiometry) and were examined for anthropometric parameters (weight, hip/height ratio, abdominal girth, etc.) and glycolipid metabolism-related parameters (insulin, blood glucose, cholesterol, etc.) between the two groups. It was suggested that hip/height ratio may be effective in determining obesity and insulin levels were associated with obesity as in healthy subjects. On the other hand, ACH-specific obesity-related factors could not be identified by examining adipocytes differentiated from disease-specific iPS cells.

Free Research Field

小児科学

Academic Significance and Societal Importance of the Research Achievements

線維芽細胞増殖因子受容体3型（FGFR3）異常を病因とするACHでは生活上問題となる疾患関連合併症が多く、肥満はその一つであり他の合併症の増悪因子でもある。ACH小児において適正体重の維持は将来のメタボリック症候群のリスクを減らしQOL改善につながると考える。本研究で認めた臀囲/身長比と体脂肪率との相関性は、身長体重を用いた肥満度に代わり臀囲/身長比がACH小児の肥満判定に有用な身体計測値である可能性を示しており、ACH小児の治療管理に役立つと考える。一方FGFシグナルとメタボリズム調節因子との関連は報告されているが脂肪細胞に対してFGFR3異常が及ぼす影響については更なる検討が必要である。