OGT suppresses macrophage proinflammatory activation

Overnutrition leads to metabolic disorders such as obesity and diabetes. Enhanced inflammation has also been shown to be an essential player in the progression of metabolic diseases. However, how immune cells sense nutritional status and contribute to whole-body metabolism remain largely elusive. OGT-catalyzed protein O-GlcNAcylation is thought to be a metabolic sensor that modulates cell signaling. In this study, we show that overnutrition stimulates macrophage O-GlcNAc signaling. O-GlcNAc signaling suppresses macrophage proinflammatory activation and protects against diet-induced obesity and metabolic dysfunction. These findings thus identify macrophage O-GlcNAc signaling as a novel homeostatic regulator at the interface of inflammation and metabolism. Unstimulated (M0), LPS (100 ng/ml, 12 hours)-stimulated (M1) and IL-4 (10 ng/ml, 12 hours)-stimulated (M2) WT and OGT knockout (KO) mouse bone marrow-derived macrophages (BMDMs) were collected. Then total RNA was extracted and used for RNA sequencing-based transcriptional profiling.