The Role of Macrophage GLUT1-Mediated Glucose Metabolism in Atherosclerosis

Macrophages play a key role in the pathogenesis of atherosclerosis. We recently created a novel murine model with GLUT1 specifically deleted from monocyte/macrophages. Preliminary results from our lab suggest that macrophages lacking GLUT1 reduce the pro-inflammatory response. We therefore hypothesized that macrophages with GLUT1 deletion will have reduced pro-inflammatory activation during atherogenesis, which will reduce formation of atherosclerosis in a mouse model lacking the LDL receptor (Ldlr-/-). We transplanted bone marrow from Glut1fl/fl or Glut1MΦ-/- mice into Ldlr-/- mice and fed mice a Western Diet (WD) for 12 weeks. Glut1MΦ-/- Ldlr-/- mice exhibited significantly less plasma total cholesterol and LDL cholesterol compared to Glut1fl/fl Ldlr-/- mice. Additionally, our results demonstrated that mice with macrophages lacking GLUT1 displayed more and larger necrotic cores in atherosclerotic lesions compared to floxed transplanted controls. These results suggest that macrophage glucose metabolism mediates systemic cholesterol metabolism, and atherogenesis. Importantly, the maintenance of atherosclerotic lesion stability may be regulated by macrophage glucose metabolism-dependent mechanisms.