Obesity resistance and increased energy expenditure by white adipose tissue browning in Oga ^sup +/-^ mice

• Published in: Diabetologia Vol. 58; no. 12; p. 2867
• Main Authors: Yang, Yong Ryoul, Jang, Hyun-jun, Choi, Sun-sil, Lee, Yong Hwa, Lee, Gyun Hui, Seo, Young-kyo, Choi, Jang Hyun, Park, Dohyun, Koh, Ara, Kim, Il Shin, Lee, Ho, Ryu, Sung Ho, Suh, Pann-ghill
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.12.2015
• Subjects: Adipocytes; Body fat; Cancer; Diabetes; Energy; Glucose; Insulin resistance; Laboratory animals; Metabolism; NMR; Nuclear magnetic resonance; Obesity; Proteins; Science; Thermogenesis; Transcription factors; South Korea; United States > US
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-015-3736-z

Aims/hypothesis O-GlcNAcylation plays a role as a metabolic sensor regulating cellular signalling, transcription and metabolism. Transcription factors and signalling pathways related to metabolism are modulated by N-acetyl-glucosamine (O-GlcNAc) modification. Aberrant regulation of O-GlcNAcylation is closely linked to insulin resistance, type 2 diabetes and obesity. Current evidence shows that increased O-GlcNAcylation negatively regulates insulin signalling, which is associated with insulin resistance and type 2 diabetes. Here, we aimed to evaluate the effects of Oga (also known as Mgea5) haploinsufficiency, which causes hyper-O-GlcNAcylation, on metabolism. Methods We examined whether Oga ^sup +/-^ mice developed insulin resistance. Metabolic variables were determined including body weight, glucose and insulin tolerance, metabolic rate and thermogenesis. Results Oga deficiency does not affect insulin signalling even at hyper-O-GlcNAc levels. Oga ^sup +/-^ mice are lean with reduced fat mass and improved glucose tolerance. Furthermore, Oga ^sup +/-^ mice resist high-fat diet-induced obesity with ameliorated hepatic steatosis and improved glucose metabolism. Oga haploinsufficiency potentiates energy expenditure through the enhancement of brown adipocyte differentiation from the stromal vascular fraction of subcutaneous white adipose tissue (WAT). Conclusions/interpretation Our observations suggest that O-GlcNAcase (OGA) is essential for energy metabolism via regulation of the thermogenic WAT program.