Interferon-gamma induced adipose tissue inflammation is linked to endothelial dysfunction in type 2 diabetic mice.

ABSTRACT: Interferon-gamma (IFN?) has previously been associated with immuno-mediated inflammation in diet-induced obesity and type 1 diabetes. This study sought to define the role of IFN?-induced adipose tissue inflammation in endothelial dysfunction in type 2 diabetes. We examined mesenteric adipose tissue (MAT) inflammation, and endothelial function of small mesenteric artery (SMA) in control mice (m Lepr(db)), diabetic mice (Lepr(db)), m Lepr(db) treated with IFN?, and Lepr(db) treated with anti-IFN? or anti-monocyte chemoattractant protein-1 (anti-MCP-1). mRNA and protein expression of IFN? and MCP-1 were increased in MAT of Lepr(db), accompanied by increased T-lymphocyte and macrophage infiltration. Anti-IFN? reduced MAT inflammatory cell infiltration and inflammatory cytokine expression in Lepr(db), while IFN? treatment showed the opposite effects in m Lepr(db). Acetylcholine (ACh)-induced vasorelaxation of SMA was impaired in Lepr(db) versus m Lepr(db), but sodium nitroprusside (SNP)-induced vasorelaxation was comparable. Both anti-IFN? and anti-MCP-1 improved endothelial function of Lepr(db), while IFN? treatment impaired endothelial function of m Lepr(db). Superoxide production was higher in both MAT and SMA of Lepr(db) mice, and anti-IFN? reduced MAT and SMA superoxide production. Macrophage accumulation in the adventitia of SMA, and mRNA expression of MCP-1 in SMA were increased in Lepr(db) and IFN?-treated m Lepr(db), but reduced in anti-IFN? treated Lepr(db). These findings suggest IFN? has a key role in the regulation of visceral adipose tissue inflammatory response and endothelial dysfunction in type 2 diabetes.

SUBMITTER: Zhang H 

PROVIDER: S-EPMC3947811 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature