Obesity resistance and increased energy expenditure by white adipose tissue browning in Oga(+/-) mice.
OBJECTIVE
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
Our observations suggest that O-GlcNAcase (OGA) is essential for energy metabolism via regulation of the thermogenic WAT program.
School of Life Sciences, Ulsan National Institute of Science and Technology, Building 104, Room 705, UNIST-gil 50, Eonyang-eup, Ulju-gun, Ulsan, 689-798, Republic of Korea.
Yong Ryoul
YR
Yang
School of Life Sciences, Ulsan National Institute of Science and Technology, Building 104, Room 705, UNIST-gil 50, Eonyang-eup, Ulju-gun, Ulsan, 689-798, Republic of Korea.|Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, Republic of Korea.
Hyun-Jun
HJ
Jang
School of Life Sciences, Ulsan National Institute of Science and Technology, Building 104, Room 705, UNIST-gil 50, Eonyang-eup, Ulju-gun, Ulsan, 689-798, Republic of Korea.
Sun-Sil
SS
Choi
School of Life Sciences, Ulsan National Institute of Science and Technology, Building 104, Room 705, UNIST-gil 50, Eonyang-eup, Ulju-gun, Ulsan, 689-798, Republic of Korea.
Yong Hwa
YH
Lee
School of Life Sciences, Ulsan National Institute of Science and Technology, Building 104, Room 705, UNIST-gil 50, Eonyang-eup, Ulju-gun, Ulsan, 689-798, Republic of Korea.
Gyun Hui
GH
Lee
School of Life Sciences, Ulsan National Institute of Science and Technology, Building 104, Room 705, UNIST-gil 50, Eonyang-eup, Ulju-gun, Ulsan, 689-798, Republic of Korea.
Young-Kyo
YK
Seo
School of Life Sciences, Ulsan National Institute of Science and Technology, Building 104, Room 705, UNIST-gil 50, Eonyang-eup, Ulju-gun, Ulsan, 689-798, Republic of Korea.
Jang Hyun
JH
Choi
Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, Republic of Korea.
Dohyun
D
Park
Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, Republic of Korea.
Ara
A
Koh
School of Life Sciences, Ulsan National Institute of Science and Technology, Building 104, Room 705, UNIST-gil 50, Eonyang-eup, Ulju-gun, Ulsan, 689-798, Republic of Korea.
Il Shin
IS
Kim
Cancer Experimental Resources Branch, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
Ho
H
Lee
Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, Republic of Korea.
Sung Ho
SH
Ryu
School of Life Sciences, Ulsan National Institute of Science and Technology, Building 104, Room 705, UNIST-gil 50, Eonyang-eup, Ulju-gun, Ulsan, 689-798, Republic of Korea. pgsuh@unist.ac.kr.
Pann-Ghill
PG
Suh
D000117:Acetylglucosamine / Q000378:metabolism; D052437:Adipocytes, Brown / Q000378:metabolism / Q000473:pathology; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000235:genetics; D002454:Cell Differentiation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D018149:Glucose Intolerance / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics*; D015398:Signal Transduction; D022722:Thermogenesis / Q000235:genetics; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
D001786:Blood Glucose; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D000117:Acetylglucosamine
Adipose tissue browning; Beige adipocyte; O-GlcNAcase; O-GlcNAcylation; Obesity; Thermogenesis