INVESTIGADORES
JEREZ Susana Josefina
artículos
Título:
High fat diet-induced metabolically obese and normal weight rabbit model shows early vascular dysfunction: mechanisms involved
Autor/es:
ALARCĂ“N, GABRIELA; ROCO, JULIETA; MEDINA, ANALIA; MEDINA, MIRTA; PERAL DE BRUNO, MARIA; JEREZ, SUSANA
Revista:
INTERNATIONAL JOURNAL OF OBESITY
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Año: 2018 vol. 42 p. 1535 - 1543
ISSN:
0307-0565
Resumen:
Background: Obesity contributes significantly to the development and evolution of cardiovascular disease (CVD) which is believed to be mediated by oxidative stress, inflammation and endothelial dysfunction. However, the vascular health of metabolically obese and normal weight (MONW) individuals is not completely comprehended.Objectives: the purpose of our study was to evaluate vascular function on the basis of a high fat diet (HFD)-MONW rabbit model. Subjects: twenty four male rabbits were fed, on the one hand, a regular diet (CD), and on the other hand an 18% extra fat on the regular diet (HFD) during 6 weeks.Results: body weight, TBARS and Gluthathione serum levels were similar between the groups; fasting glucose, triglycerides, C reactive protein (CRP), visceral adipose tissue, triglyceride-glucose index (T y G index) were higher in the HFD group. Compared to CD, the HFD rabbits had glucose intolerance and lower HDL-cholesterol and plasma nitrites levels. Thoracic aortic rings from HFD rabbits exhibited: a) a reduced acetylcholine-induced vasorelaxation; b) a greater contractile response to norepinephrine and KCl; c) an improved angiotensin II- sensibility. The HFD-effect on acetylcholine-response was reversed by NS398 (cyclooygenase-2 inhibitor) and SC560 (cyclooxygenase-1 inhibitor), and the HFD-effect on angiotensin II was reversed by NS398 and SQ 29538 (TP receptor blocker). Immunohistochemistry and western blot studies showed cyclooxygenase-2 expression only in arteries from HFD rabbits.Conclusions: our study shows a positive pro-inflammatory status of HFD-induced MONW characterized by the cyclooxygenase-2 expression, increase of the CRP levels, reduction of NO release and oxidative stress-controlled conditions in an early stage of metabolic alterations characteristic of metabolic syndrome. Endothelial dysfunction and increased vascular reactivity in MONW individuals may be biomarkers of early vascular injury. Therefore, the metabolic changes induced by HFD even in normal weight individuals may be associated to functional alterations of blood vessels.