OGT suppresses S6K1-mediated macrophage inflammation and metabolic disturbance.
Proc Natl Acad Sci U S A
; 117(28): 16616-16625, 2020 07 14.
Article
in En
| MEDLINE
| ID: mdl-32601203
ABSTRACT
Enhanced inflammation is believed to contribute to overnutrition-induced metabolic disturbance. Nutrient flux has also been shown to be essential for immune cell activation. Here, we report an unexpected role of nutrient-sensing O-linked ß-N-acetylglucosamine (O-GlcNAc) signaling in suppressing macrophage proinflammatory activation and preventing diet-induced metabolic dysfunction. Overnutrition stimulates an increase in O-GlcNAc signaling in macrophages. O-GlcNAc signaling is down-regulated during macrophage proinflammatory activation. Suppressing O-GlcNAc signaling by O-GlcNAc transferase (OGT) knockout enhances macrophage proinflammatory polarization, promotes adipose tissue inflammation and lipolysis, increases lipid accumulation in peripheral tissues, and exacerbates tissue-specific and whole-body insulin resistance in high-fat-diet-induced obese mice. OGT inhibits macrophage proinflammatory activation by catalyzing ribosomal protein S6 kinase beta-1 (S6K1) O-GlcNAcylation and suppressing S6K1 phosphorylation and mTORC1 signaling. These findings thus identify macrophage O-GlcNAc signaling as a homeostatic mechanism maintaining whole-body metabolism under overnutrition.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
N-Acetylglucosaminyltransferases
/
Ribosomal Protein S6 Kinases, 90-kDa
/
Macrophages
/
Obesity
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Year:
2020
Type:
Article