Imbalance between pro and anti-oxidant mechanisms in perivascular adipose tissue aggravates long-term high-fat diet-derived endothelial dysfunction.
BACKGROUND
The hypothesis of this study is that long-term high-fat diets (HFD) induce perivascular adipose tissue (PVAT) dysfunction characterized by a redox imbalance, which might contribute to aggravate endothelial dysfunction in obesity.


RESULTS
C57BL/6J mice were fed either control or HFD (45% kcal from fat) for 32 weeks. Body weight, lumbar and mesenteric adipose tissue weights were significantly higher in HFD animals compared to controls. The anticontractile effect of PVAT in mesenteric arteries (MA) was lost after 32 week HFD and mesenteric endothelial-dependent relaxation was significantly impaired in presence of PVAT in HFD mice (Emax = 71.0±5.1 vs Emax = 58.5±4.2, p<0.001). The inhibitory effect of L-NAME on Ach-induced relaxation was less intense in the HFD group compared with controls suggesting a reduction of endothelial NO availability. Expression of eNOS and NO bioavailability were reduced in MA and almost undetectable in mesenteric PVAT of the HFD group. Superoxide levels and NOX activity were higher in PVAT of HFD mice. Apocynin only reduced contractile responses to NA in HFD animals. Expression of ec-SOD and total SOD activity were significantly reduced in PVAT of HFD mice. No changes were observed in Mn-SOD, Cu/Zn-SOD or catalase. The ratio [GSSG]/([GSH]+[GSSG]) was 2-fold higher in the mesenteric PVAT from HFD animals compared to controls.


CONCLUSIONS
We suggest that the imbalance between pro-oxidant (NOX, superoxide anions, hydrogen peroxide) and anti-oxidant (eNOS, NO, ecSOD, GSSG) mechanisms in PVAT after long-term HFD might contribute to the aggravation of endothelial dysfunction.
Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain.
Marta
M
Gil-Ortega
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Luis
L
Condezo-Hoyos
Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain.
Concha F
CF
García-Prieto
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Silvia M
SM
Arribas
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
M Carmen
MC
González
Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Isabel
I
Aranguez
Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain.
Mariano
M
Ruiz-Gayo
Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain.
Beatriz
B
Somoza
Instituto Pluridisciplinar y Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
María S
MS
Fernández-Alfonso
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010084:Oxidation-Reduction; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III