Significance of novel ubiqutin ligase of SREBP in obesity, diabetes and Cushing syndrome

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08554
• 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: Osaka University
• Principal Investigator: Okuno Yosuke 大阪大学, 大学院医学系研究科, 助教 (10534513)
• Co-Investigator(Kenkyū-buntansha): 大月 道夫 大阪大学, 医学系研究科, 准教授 (00403056) ; 福原 淳範 大阪大学, 大学院医学系研究科, 寄附講座准教授 (00437328)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ARMC5

Outline of Final Research Achievements

Fatty acid desaturation was impaired in the WAT of adipocyte-specific Armc5 knockout mice. Increased mesenteric adiposity was due to adipocyte hyperplasia. ATAC-Seq peaks were diminished around the Scd1 locus in adipocyte-specific Armc5 knockout mice.
Full-length SREBF1 were decreased in SCAP-deficient CHO cells, which was rescued by additional knockout of ARMC5. Overexpression of SCAP inhibited ARMC5-mediated degradaion of full-length SREBF1 and increased the ration of nuclear SREBF1/full-length SREBF1.

Free Research Field

脂肪細胞学

Academic Significance and Societal Importance of the Research Achievements

これまでin vitroでの機能のみが解明されていたARMC5が、in vivoの脂肪組織においてSREBF1の活性に必須であり、脂肪酸不飽和化や内臓脂肪蓄積を制御すること、また、これがSCAP非結合型SREBF1の分解によることを明らかにした。
本研究により、内臓脂肪蓄積の新たな制御機構が明らかとなり、内臓脂肪蓄積抑制薬の開発につながる可能性がある。