Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09743
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Satoshi Ugi 滋賀医科大学, 医学部, 講師 (20378483)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: O-GlcNAc修飾 / 褐色脂肪細胞 / 熱産生 / ミトコンドリア / 肥満

Outline of Final Research Achievements

The aim of study was to investigate the critical role of O-linked N-acetylglucosamine (O-GlcNAc ) modification in cold-induced thermogenesis. Deletion of Ogt in brown adipose tissue (BAT) resulted in severe cold intolerance with decreased Ucp1 expression. Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased PGC-1α protein expression, suggesting that O-GlcNAc modification in BAT is responsible for cold-induced thermogenesis. Hypothermia was significant under fasting conditions. This effect was mitigated after normal diet consumption but not after consumption of a ketogenic diet lacking carbohydrates, suggesting impaired diet-induced thermogenesis, particularly by fat. In conclusion, O-GlcNAc modification is essential for cold-induced thermogenesis and mitochondrial biogenesis in BAT. Glucose flux into BAT may be a signal to maintain BAT physiological responses.

Free Research Field

糖尿病学

Academic Significance and Societal Importance of the Research Achievements

褐色脂肪組織はマウスには存在するが成人では存在しないと最近まで考えられていたが、成人においても存在することが明らかになり、大きな注目を浴びている。本研究により、O-GlcNAc修飾が、褐色脂肪において、ミトコンドリアバイオジェネシスを介して熱産生を調節していることが明らかになった。このことから、O-GlcNAc修飾を調節することにより、褐色脂肪細胞を活性化させ、熱産生を増加させることにより、肥満の予防、治療法の開発につながる可能性がある。