Obesity resistance and increased energy expenditure by white adipose tissue browning in Oga(+/-) mice.

Abstract

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(+/-) 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(+/-) mice are lean with reduced fat mass and improved glucose tolerance. Furthermore, Oga(+/-) 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.

• Authors: Yong Ryoul Yang, Hyun-Jun Jang, Sun-Sil Choi, Yong Hwa Lee, Gyun Hui Lee, Young-Kyo Seo, Jang Hyun Choi, Dohyun Park, Ara Koh, Il Shin Kim, Ho Lee, Sung Ho Ryu, Pann-Ghill Suh
• Journal: Diabetologia (Diabetologia) Vol. 58 Issue 12 Pg. 2867-76 (Dec 2015) ISSN: 1432-0428 [Electronic] Germany
• PMID: 26342595 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• hexosaminidase C
• beta-N-Acetylhexosaminidases
• Acetylglucosamine

Topics

• Acetylglucosamine (metabolism)
• Adipocytes, Brown (metabolism, pathology)
• Adipose Tissue, Brown (metabolism)
• Adipose Tissue, White (metabolism)
• Animals
• Blood Glucose (metabolism)
• Body Weight (genetics)
• Cell Differentiation
• Diabetes Mellitus, Type 2 (genetics)
• Energy Metabolism (genetics)
• Glucose Intolerance (genetics)
• Insulin Resistance (genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Obesity (genetics)
• Signal Transduction
• Thermogenesis (genetics)
• beta-N-Acetylhexosaminidases (genetics)