Macrophage Migration Inhibitory Factor Deficiency Ameliorates High-Fat Diet Induced Insulin Resistance in Mice with Reduced Adipose Inflammation and Hepatic Steatosis

摘要: Macrophage infiltration is a critical determinant of high-fat diet induced adipose tissue inflammation and insulin resistance. The precise mechanisms underpinning the initiation macrophage recruitment activation are unclear. migration inhibitory factor (MIF), pro-inflammatory cytokine, displays chemokine-like properties. Circulating MIF levels elevated during obesity however its role in resistance remains elusive. Wildtype MIF-/- C57Bl\6J mice were fed chow or diet. Body weight food intake was assessed. Glucose homeostasis monitored by glucose tolerance tests. Adipose sensitivity evaluated. Cytokine secretion from stromal vascular fraction, explants bone marrow macrophages measured. Inflammatory signature 3T3-L1-adipocytes co-cultured with wildtype quantified. Hepatic triacylglyceride exhibited reduced gain. Age weight-matched obese improved coincident M1 infiltration. Obese fraction secreted less TNFα greater IL-10 compared to wildtype. Activation JNK impaired MIF-/-adipose, concomitant pAKT expression. cultured had cytokine sensitivity, effects which also attained inhibitor ISO-1. liver hepatic triacyglyceride accumulation, enhanced expression NFκB activation. deficiency partially protects attenuating infiltration, ameliorating inflammation, adipocyte ex vivo. represents potential therapeutic target for treatment