Periadventitial adipose tissue promotes endothelial dysfunction via oxidative stress in diet-induced obese C57Bl/6 mice.
BACKGROUND
Biological substances derived from perivascular fat modulate vascular tone, thus alterations in periadventitial adipose tissue (PVAT) may aggravate endothelial dysfunction in obesity.


RESULTS
Male C57Bl/6 mice were fed either a high-fat diet or standard laboratory chow for 8 months. Vascular responses were studied in organ bath chambers from abdominal aortic ring preparations in the absence or presence of PVAT. The amount of PVAT as well as the cross-sectional area of adipocytes were increased in obese mice. In the presence of PVAT, obese aortas displayed impaired endothelium-dependent vasodilation whereas endothelium-independent vasodilatation was unaltered. Endothelium-dependent vasodilatation was restored after removal of PVAT and after reducing superoxide and hydrogen peroxide formation in the vascular wall by Tiron or polyethylene-glycol-catalase, respectively. PVAT from obese mice showed increased formation of hydrogen peroxide and superoxide. The PVAT-derived oxidative stress was abolished by pretreatment with the reduced nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase inhibitor, apocynin. The anti-contractile function of PVAT found in lean mice was completely abolished in obese mice, but partially restored after pretreatment with Tiron. The mRNA expressions of monocyte chemotactic protein-1, leptin and NADPH oxidase were markedly higher in the PVAT of obese than lean mice.


CONCLUSIONS
PVAT promotes endothelial dysfunction in diet-induced obese C57Bl/6 mice via mechanisms that are linked to increased NADPH oxidase-derived oxidative stress and increased production of pro-inflammatory cytokines.
School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Juha
J
Ketonen
Jin
J
Shi
Essi
E
Martonen
Eero
E
Mervaala
D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000503:physiopathology*; D000818:Animals; D001011:Aorta / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004032:Diet / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress; D014664:Vasodilation
D016207:Cytokines; D019255:NADPH Oxidases