Dietary obesity in the rat induces endothelial dysfunction without causing insulin resistance: a possible role for triacylglycerols

Abstract

Impaired arterial vasorelaxation, due primarily to endothelial dysfunction, is associated with obesity. To clarify the relationship with insulin resistance and other metabolic disturbances, we studied endothelial-dependent and -independent vascular responses in rats with dietary-induced obesity. Dietary-obese rats had significantly higher body weights (10-32%; P<0.001) and fat-pad masses (220-280%; P<0.001) than lean controls, together with raised plasma levels of triacylglycerols (15-80%; P<0.001), non-esterified fatty acids (13-38%; P<0.05) and leptin (85-180%; P<0.001). However, measures of insulin sensitivity (including the hyperinsulinaemic-euglycaemic clamp in a parallel experiment) were comparable with those in controls. Contractions induced in mesenteric arteries by noradrenaline (0.5-8 micromol/l) were comparable in lean and obese groups, but vasorelaxation in noradrenaline-preconstricted arteries was markedly reduced in dietary-obese rats of both sexes. Concentration-response curves to endothelium-dependent vasorelaxants (acetylcholine, A23187 and insulin) showed significant reductions in maximal relaxation (20-95% less than in leans; P<0.001) and significant rightward shifts in EC(40) (concentration giving 40% of maximal response) (P<0.01). Relaxation in response to the direct NO donor, sodium nitroprusside, showed a lesser impairment (12%; P<0.01) in dietary-obese rats. Maximal relaxation to acetylcholine was correlated inversely in both sexes with fat-pad mass (r(2)=0.37, P<0.05) and plasma triacylglycerols (r(2)=0.51, P<0.01), and with leptin in males only (r(2)=0.35, P<0.05). Independent determinants of acetylcholine-induced relaxation were fat mass and plasma triacylglycerols; plasma insulin and insulin sensitivity had no effect. Dietary-induced obesity severely impaired arterial relaxation in both sexes, particularly at the endothelial level. This is not attributable to insulin resistance, but may be related to moderate hypertriglyceridaemia.

White tea (Camellia sinensis) extract reduces oxidative stress and triacylglycerols in obese mice

“…Hypertriacylglycerolemia also leads to endothelial dysfunction contributing to atherogenesis (NADERALI et al, 2001). Moreover, the increased oxidative stress, itself, is a risk factor for cardiovascular diseases (VOGIATZI; TOUSOULIS; STEFANADIS, 2009).…”

Alterações vasculares em ratos obesos por dieta rica em gordura: papel da Via L-arginina/NO Endotelial

“…For example, high-fat diet impairs endotheliumdependent vasorelaxation 23,24 . This may, at least in part, explain the increased risk of vascular disease in obese subject and animals.…”

Enhanced vascular contractility and diminished coronary artery flow in rats made hypertensive from diet-induced obesity

“…[10][11][12][13][14][15] However, human obesity primarily results from alterations in a combination of different genes (i.e., polygenic) that interact with environmental factors such as diet to promote aspects of the metabolic syndrome. Outbred Sprague-Dawley rats respond to a moderately high fat (MHF) diet with either an obesityprone (OP) or obesity-resistant (OR) phenotype.…”

“…Endothelial dysfunction has been previously defined in blood vessels from rodent models of diet-induced obesity. 13 The purpose of this study was to determine whether vascular contractile responses to several different agonists were enhanced in mesenteric resistance arteries from rats with diet-induced obesity and hypertension. Moreover, we examined cardiac contractile function and coronary artery perfusion pressure in isolated hearts from rats with diet-induced obesity and hypertension.…”