CC Chemokine Receptor 2 Promotes Recruitment of Myeloid Cells Associated with Insulin Resistance in Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a common disease, closely associated with obesity and insulin resistance. We investigated the presence of a subset of myeloid cells associated with metabolic disturbance in the liver of patients with NAFLD and a murine model of obesity-induced liver disease. Gene and protein expression in liver and serum was investigated with rt-PCR or ELISA and correlated to clinical disease. Liver-infiltrating immune cells were isolated from normal or diseased human liver for flow cytometric analysis. In animal experiments, mice were fed a high-fat diet (60% of calories from fat) for 16 weeks, or high-fat diet with 30% fructose for 32 weeks to induce steatohepatitis and fibrosis. A small molecule inhibitor of CCR2, CCX872, was administered to some mice. A subset of CD11c+CD206+ immune cells were enriched in human liver tissue, and greater infiltration was observed in NAFLD. The presence of CD11c+CD206+ myeloid cells correlated with systemic insulin resistance. CD11c+CD206+ ce...