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- Title
Pivotal Role of -GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis.
- Authors
Natsuko Ohashi; Katsutaro Morino; Shogo Ida; Osamu Sekine; Mengistu Lemecha; Shinji Kume; Shi-Young Park; Cheol Soo Choi; Satoshi Ugi; Hiroshi Maegawa; Ohashi, Natsuko; Morino, Katsutaro; Ida, Shogo; Sekine, Osamu; Lemecha, Mengistu; Kume, Shinji; Park, Shi-Young; Choi, Cheol Soo; Ugi, Satoshi; Maegawa, Hiroshi
- Abstract
Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown (BAT) adipose tissue play significant roles in lipid and glucose metabolism. O-linked N-acetylglucosamine (O-GlcNAc) modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. However, little is known about the role of O-GlcNAc modification in adipose tissues. Here, we report the critical role of O-GlcNAc modification in cold-induced thermogenesis. Deletion of Ogt in WAT and BAT using adiponectin promoter-driven Cre recombinase resulted in severe cold intolerance with decreased uncoupling protein 1 (Ucp1) expression. Furthermore, Ogt deletion led to decreased mitochondrial protein expression in conjunction with decreased peroxisome proliferator-activated receptor γ coactivator 1-α protein expression. This phenotype was further confirmed by deletion of Ogt in BAT using Ucp1 promoter-driven Cre recombinase, 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 fatty acid-rich 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.
- Subjects
ADIPOSE tissues; GLUCOSE metabolism; TRANSFERASES; PEROXISOME proliferator-activated receptors; MITOCHONDRIAL DNA; ADIPOSE tissue physiology; MITOCHONDRIAL physiology; RNA metabolism; PHYSIOLOGICAL adaptation; ANIMAL experimentation; BODY temperature regulation; COLD (Temperature); GENES; MICE; RNA; GLUCOSAMINE
- Publication
Diabetes, 2017, Vol 66, Issue 9, p2351
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db16-1427