title: 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 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.
authors.affiliation: Department of Internal Medicine, Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, MO 65211, USA.
authors.forename: Hanrui
authors.initials: H
authors.lastname: Zhang
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Potter
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Cao
authors.forename: Cuihua
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D007371:Interferon-gamma / Q000378:metabolism*; D050152:Intra-Abdominal Fat / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D008638:Mesenteric Arteries / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008643:Mesentery / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D060888:Real-Time Polymerase Chain Reaction; D014664:Vasodilation / Q000502:physiology
chemical_list: D007371:Interferon-gamma