Systemic inflammation and insulin sensitivity in obese IFN-gamma knockout mice

作者：O' Rourke Robert W; White Ashley E; Metcalf Monja D; Winters Brian R; Diggs Brian S; Zhu Xinxia; Marks Daniel L

来源：Metabolism-Clinical and Experimental, 2012, 61(8): 1152-1161.

DOI：10.1016/j.metabol.2012.01.018

Adipose tissue macrophages are important mediators of inflammation and insulin resistance in obesity. IFN-gamma is a central regulator of macrophage function. The role of IFN-gamma in regulating systemic inflammation and insulin resistance in obesity is unknown. We studied obese IFN-gamma knockout mice to identify the role of IFN-gamma in regulating inflammation and insulin sensitivity in obesity. IFN-gamma-knockout C578116 mice and wild-type control litter mates were maintained on normal chow or a high fat diet for 13 weeks and then underwent insulin sensitivity testing then sacrifice and tissue collection. Flow cytometry, intracellular cytokine staining, and QRTPCR were used to define tissue lymphocyte phenotype and cytokine expression profiles. Adipocyte size was determined from whole adipose tissue explants examined under immunofluorescence microscopy. Diet-induced obesity induced systemic inflammation and insulin resistance, along with a pan-leukocyte adipose tissue infiltrate that includes macrophages, T-cells, and NK cells. Obese IFN-gamma-knockout animals, compared with obese wild-type control animals, demonstrate modest improvements in insulin sensitivity, decreased adipocyte size, and an M2-shift in ATM phenotype and cytokine expression. These data suggest a role for IFN-gamma in the regulation of inflammation and glucose homeostasis in obesity though multiple potential mechanisms, including effects on adipogenesis, cytokine expression, and macrophage phenotype.

• 出版日期2012-8