Macrophage Deletion of SOCS1 Increases Sensitivity to LPS and Palmitic Acid and Results in Systemic Inflammation and Hepatic Insulin Resistance

摘要: OBJECTIVE Macrophage secretion of proinflammatory cytokines contributes to the pathogenesis obesity-related insulin resistance. An important regulator inflammation is suppressor cytokine signaling-1 (SOCS1), which inhibits JAK-STAT and toll-like receptor-4 (TLR4) pathways. Despite reported role SOCS1 in inhibiting signaling, it surprising that a polymorphism increases promoter activity associated with enhanced sensitivity despite obesity. In current study, we investigated physiological myeloid lymphoid cell regulating sensitivity. RESEARCH DESIGN AND METHODS We used mice generated by crossing floxed expressing Cre recombinase under control LysM-Cre (SOCS1 LysM-cre ). These have deletion macrophages lymphocytes. assessed macrophage using flow cytometry serum levels Bioplex assays. then measured glucose tolerance tests euglycemic-hyperinsulinemic clamp. Using bone marrow–derived macrophages, tested effects responses TLR4 ligands: lipopolysaccharide (LPS) palmitic acid. RESULTS had increased expression CD11c, LPS, acid concentrations tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein. Increased was impaired hyperinsulinemia as result reduced hepatic but not skeletal muscle CONCLUSIONS The hematopoietic cells protects against systemic resistance potentially LPS palmitate-induced signaling macrophages.