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.

Effects of diet-induced obesity on protein expression in insulin signaling pathways of skeletal muscle in male Wistar rats

“…Furthermore, a number of studies have reported a lack of impact of reduction in fatty acid oxidation on increasing accumulation of fatty acyl-CoA (a triacylglyceride intermediate) in muscle 13,17,18. The increased plasma triacylglyceride levels seen in this study and in previous reports3,19 suggest that it is reasonable to hypothesize a role of increased lipid uptake into muscle in subjects with diet-induced obesity and ultimately development of diet-induced diabetes. Interestingly, both methods of weight reduction (long-term removal of a highly palatable diet and administration of fenofibrate) caused marked reduction of elevated levels of intramuscular and plasma triacylglycerides.…”

High-fat diet increases O-GlcNAc levels in cerebral arteries: a link to vascular dysfunction associated with hyperlipidaemia/obesity?

“…Vascular dysfunction induced by high intake of fat occurs either in the presence [32] or absence of obesity [33], indicating that high fat, per se, leads to vascular dysfunction. In the present study, we show that a 12-week HFD augmented corporal weight and plasma triglycerides while cholesterol, blood glucose and insulin concentrations were not changed.…”

Anti-proliferative and angio-suppressive effect ofStoechospermum marginatum(C. Agardh) Kutzing extract using various experimental models

“…3 [H] Thymidine incorporation assay was performed as described previously [26]. In brief, the tumor cells were plated onto 12-well culture plates at 25 × 10 3 cells/well and incubated at 37℃ in 5% CO 2 for 48 hrs in DMEM medium.…”