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 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 Leprdb), diabetic mice (Leprdb), m Leprdb treated with IFNγ, and Leprdb 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 Leprdb, accompanied by increased T-lymphocyte and macrophage infiltration. Anti-IFNγ reduced MAT inflammatory cell infiltration and inflammatory cytokine expression in Leprdb, while IFNγ treatment showed the opposite effects in m Leprdb. Acetylcholine (ACh)-induced vasorelaxation of SMA was impaired in Leprdb versus m Leprdb, but sodium nitro-prusside (SNP)-induced vasorelaxation was comparable. Both anti-IFNγ and anti-MCP-1 improved endothelial function of Leprdb, while IFNγ treatment impaired endothelial function of m Leprdb. Superoxide production was higher in both MAT and SMA of Leprdb 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 Leprdb and IFNγ-treated m Leprdb, but reduced in anti-IFNγ treated Leprdb. These findings suggest IFNγ has a key role in the regulation of visceral adipose tissue inflammatory response and endothelial dysfunction in type 2 diabetes.

Effect of Supervised Lifestyle Changes on Metabolic Syndrome-Associated Inflammation

“…There were no gender- related differences in the hsCRP levels during the study. IFN-γ plays a major role in inflammation of adipose tissue and vascular dysfunction (31)(32)(33). Our results confirmed previously published data about the proinflammatory roles of this cytokine.…”

Adiponectin abates diabetes-induced endothelial dysfunction by suppressing oxidative stress, adhesion molecules, and inflammation in type 2 diabetic mice

“…Relative amounts of protein expression were quantified and normalized to those of the corresponding internal reference, ␤-actin, and then subsequently normalized to corresponding CON mice, which were set to a value of 1.0. The specificity of all antibodies has been demonstrated in our previous studies (4,23,40,51).…”

The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: an update

“…Chronic low-grade inflammation can be both a cause and consequence of endothelial dysfunction, and the two appear to be tightly linked [65]. Since type 2 diabetes is highly associated with obesity, the metabolic role of adipose tissue potentiates the adverse effects on the vasculature [31, 98, 99]. Adipose tissue secretes a range of proinflammatory molecules, which lead to systemic inflammation and participate in the cross talk between adipose stores and the vascular wall (see Ref.…”

“…Local inflammation in the vasculature is attributed to effects by the inflammatory cytokines/chemokines and leukocyte adhesion molecules expressed and released by the endothelium [97, 100]. Anti-inflammatory treatment by neutralizing antibodies to TNF α , MCP-1 and IFN γ effectively attenuated endothelial dysfunction in db/db mice without significantly affecting body weight and glucose metabolism [23, 91, 98]. This suggests that vasoprotection by anti-inflammatory therapies can be independent of their metabolic effects.…”