Elucidation of regulatory mechanisms of insulin sensitivity through a energy sensor molecule, DUSP16

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09829
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Kagoshima University
• Principal Investigator: MATSUGUCHI TETSUYA 鹿児島大学, 医歯学域歯学系, 教授 (10303629)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肥満 / メタボリックシンドローム / 脂肪細胞 / 骨芽細胞 / 間葉系幹細胞 / JNK / DUSP16 / EGR1

Outline of Final Research Achievements

Chronic inflammation associated with obesity has attracted attention as a cause of diseases such as diabetes and cancer. DUSP16 is a specific inhibitory protein of JNK, which has been revealed as a key molecule linking obesity and chronic inflammation. This study demonstrated that the expression level of DUSP16 increases with extracellular glucose concentration, and that it functions as an "energy sensor" that plays an important role in inducing GLUT4 expression. It was also found that the expression of DUSP16 increases during adipogenic differentiation of mesenchymal stem cells, and that it functions as a positive regulator of adipogenesis. Thus, this study suggests the possibility of DUSP16 as a connecting factor connecting carbohydrate and lipid metabolism with chronic inflammation.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

肥満は世界的な健康問題となっており、肥満に伴う慢性炎症が、Ⅱ型糖尿病、心血管障害、脂肪肝、一部のがんなどの発症と密接に関連する。近年の研究で、炎症性キナーゼであるJNKが肥満に伴う組織慢性炎症に必須な分子として同定され、その活性を抑制することで各種合併症を予防できることが期待される。本研究は、JNKの特異的活性抑制タンパクであるDUSP16の糖質代謝と脂肪細胞分化の制御における役割を明らかにした。肥満に伴う各種合併症の発症にDUSP16の活性異常が関わる可能性がある。