title: Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity.
abstract: Perivascular adipose tissue (PVAT) plays a paracrine role in regulating vascular tone. We hypothesize that PVAT undergoes adaptative mechanisms during initial steps of diet-induced obesity (DIO) which contribute to preserve vascular function. Four-week-old male C57BL/6J mice were assigned either to a control [low-fat (LF); 10% kcal from fat] or to a high-fat diet (HF; 45% kcal from fat). After 8 wk of dietary treatment vascular function was analyzed in the whole perfused mesenteric bed (MB) and in isolated mesenteric arteries cleaned of PVAT. Relaxant responses to acetylcholine (10(-9)-10(-4) m) and sodium nitroprusside (10(-12)-10(-5) m) were significantly ameliorated in the whole MB from HF animals. However, there was no difference between HF and LF groups in isolated mesenteric arteries devoid of PVAT. The enhancement of relaxant responses detected in HF mice was not attributable to an increased release of nitric oxide (NO) from the endothelium nor to an increased sensitivity and/or activity of muscular guanilylcyclase. Mesenteric PVAT of HF animals showed an increased bioavailability of NO, detected by 4,5-diaminofluorescein diacetate (DAF2-DA) staining, which positively correlated with plasma leptin levels. DAF-2DA staining was absent in PVAT from ob/ob mice but was detected in these animals after 4-wk leptin replacement. The main finding in this study is that adaptative NO overproduction occurs in PVAT during early DIO which might be aimed at preserving vascular function.
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Alimentación, Facultad de Farmacia, Ceu-Universidad San Pablo, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Gil-Ortega
authors.forename: Paula
authors.initials: P
authors.lastname: Stucchi
authors.forename: Rocío
authors.initials: R
authors.lastname: Guzmán-Ruiz
authors.forename: Victoria
authors.initials: V
authors.lastname: Cano
authors.forename: Silvia
authors.initials: S
authors.lastname: Arribas
authors.forename: M Carmen
authors.initials: MC
authors.lastname: González
authors.forename: Mariano
authors.initials: M
authors.lastname: Ruiz-Gayo
authors.forename: Maria S
authors.initials: MS
authors.lastname: Fernández-Alfonso
authors.forename: Beatriz
authors.initials: B
authors.lastname: Somoza
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology; D020738:Leptin / Q000097:blood; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000378:metabolism; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism*; D011863:Radioimmunoassay
chemical_list: D052242:Adiponectin; D004041:Dietary Fats; D020738:Leptin; D009599:Nitroprusside; D009569:Nitric Oxide; D000109:Acetylcholine