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

Abstract

Interferon-gamma (IFNγ) has previously been associated with immuno-mediated inflammation in dietinduced obesity and type 1 diabetes. This study sought to define the role of IFNγ-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 IFNγ, and Lepr db treated with anti-IFNγ or anti-monocyte chemoattractant protein-1 (anti-MCP-1). mRNA and protein expression of IFNγ and MCP-1 were increased in MAT of Lepr db, accompanied by increased T-lymphocyte and macrophage infiltration. Anti-IFNγ reduced MAT inflammatory cell infiltration and inflammatory cytokine expression in Lepr db, while IFNγ 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-IFNγ and anti-MCP-1 improved endothelial function of Lepr db, while IFNγ treatment impaired endothelial function of m Lepr db. Superoxide production was higher in both MAT and SMA of Lepr db mice, and anti-IFNγ 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 IFNc-treated m Lepr db, but reduced in anti-IFNγ treated Lepr db. These findings suggest IFNγ has a key role in the regulation of visceral adipose tissue inflammatory response and endothelial dysfunction in type 2 diabetes. © Springer-Verlag 2011.