Elucidation of the physiological role of O-GlcNAc modification in brown adipose tissue and search for novel therapeutic targets

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16226
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Ohashi Natsuko 滋賀医科大学, 医学部, 特任助教 (60816776)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 褐色脂肪細胞 / 白色脂肪細胞 / エネルギー代謝 / 糖代謝

Outline of Final Research Achievements

In obesity and diabetes mellitus, protein dysfunctions mediated by post-translational modifications are deeply involved in the pathogenesis and progression of the disease, and O-GlcNAc modification is one of the post-translational modifications.
In this study, we generated adipose tissue-specific Ogt-deficient mice and brown adipose tissue-specific Ogt-deficient mice, and examined them as models of diet-induced obesity and diabetes by loading them with a high-fat diet.
Loss of O-GlcNAc modification in WAT exhibited obesity resistance and impaired glucose tolerance because of lipoatrophy under diet induced obesity, and the results suggest that O-GlcNAc modification in white adipose tissue plays an important role in fatty acid synthesis and functional maturation of adipocytes during obesogenesis.

Free Research Field

糖尿病・代謝

Academic Significance and Societal Importance of the Research Achievements

O-GlcNAc修飾の異常は、糖尿病をはじめとする代謝異常や癌、アルツハイマー病などの疾患と密接に関連している。今回、白色脂肪組織のO-GlcNAc修飾は、肥満形成過程における脂肪酸合成や脂肪細胞の機能的成熟に関して重要な役割を果たしていることが明らかとなった。一方で、褐色脂肪組織のO-GlcNAc修飾に関しては、肥満形成過程においては糖代謝及び肥満に及ぼす影響は少ない結果となった。未だ解明すべき課題は残されてはいるが、肥満や糖尿病状態における各脂肪組織のO-GlcNAc修飾の意義及び役割の一部が明らかとなったことから、今後の肥満・2型糖尿病の病態機序解明への寄与が期待される。