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01-11-2011 | Original Contribution

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

Authors: Hanrui Zhang, Barry J. Potter, Ji-Min Cao, Cuihua Zhang

Published in: Basic Research in Cardiology | Issue 6/2011

Abstract

Interferon-gamma (IFNγ) has previously been associated with immuno-mediated inflammation in diet-induced 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 IFNγ-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.

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Title: Interferon-gamma induced adipose tissue inflammation is linked to endothelial dysfunction in type 2 diabetic mice
Authors: Hanrui Zhang
Barry J. Potter
Ji-Min Cao
Cuihua Zhang
Publication date: 01-11-2011
Publisher: Springer-Verlag
Published in: Basic Research in Cardiology / Issue 6/2011
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-011-0212-x

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

Abstract

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