Chronic withdrawal of a high-palatable obesity-inducing diet completely reverses metabolic and vascular abnormalities associated with dietary-obesity in the rat

Chronic consumption of a high-palatable diet induces obesity and markedly impairs arterial relaxation. We have recently reported that endothelial function is only partially resorted after acute withdrawal of palatable diet. Therefore, this study was designed to investigate the effects of chronic withdrawal of high-palatable obesity-inducing diet on metabolic and vascular function in rats. Wistar rats were fed either standard laboratory chow throughout (controls) or given a highly-palatable diet (diet-fed) for 15 weeks; or fed the diet for 8 weeks and then returned to chow (diet-to-chow) for further 7 weeks before sacrifice. Diet-fed rats had higher body weight, fat mass, liver and heart weight than both chow-fed and diet-to-chow groups (P<0.01 for all). Compared with chow-fed and diet-to-chow groups, diet-fed rats had significantly raised fasting plasma levels of insulin, leptin and triglycerides levels (each +180%; P<0.0001), but not glucose or non-esterified fatty acids. There were no significant differences between any metabolic parameters between chow-fed and diet-to-chow groups. Mesenteric arteries showed no significant differences between any groups in KCl-induced tension generation, while diet-fed groups had significantly higher noradrenaline-induced vasoconstriction than both chow-fed and diet-to-chow groups. Maximum endothelial-dependent vasorelaxation responses to carbamylcholine (CCh) were significantly (by 23%; P<0.001) attenuated in the diet-fed group. This defect was abolished in the diet-to-chow group. There were no significant differences in endothelium-independent vasorelaxation responses to sodium nitroprusside between the three groups. In conclusion, palatable diet induces obesity and metabolic abnormalities as well as a marked endothelial dysfunction. These abnormalities are completely reversed by chronic withdrawal of the obesity-inducing high-palatable diet.