Diet-induced endothelial dysfunction in the rat is independent of the degree of increase in total body weight

Abstract

A growing number of studies indicate an association between obesity, insulin resistance, dyslipidaemia and cardiovascular disorders, collectively known as Syndrome X. In this study we have aimed to produce a model of Syndrome X by voluntary feeding of Wistar rats with a highly palatable cafeteria diet, and examined its effects on metabolic changes and vascular reactivity of Wistar rats. At the end of the experiment, the cafeteria-diet fed group was divided into two groups of low weight gain (LWG) and high weight gain (HWG). Both LWG and HWG groups had significantly (P<0.01) higher fat-pad mass than their chow-fed counterparts, while gastrocnemius muscle mass were comparable. All cafeteria-diet fed rats had significantly (P<0.01) raised plasma triacylglycerol (TG) levels whereas plasma non-esterified fatty acids, glucose and insulin levels were similar between chow-fed and cafeteria-diet fed rats. Vasorelaxation responses to acteylcholine, insulin and sodium nitroprusside were significantly (P<0.01) attenuated in cafeteria-diet fed animals; however, there were no differences in contractile responses of the mesenteric arteries to noradrenaline or KCl between the groups. Multiple regression analysis showed a significant (P<0.05) negative association between plasma TG levels and reduction in acetylcholine-induced vasorelaxation. Acetylcholine-induced vasorelaxation was also significantly (P<0.05) associated with the amount of fat-pad mass. These data suggest that diet-induced vascular dysfunction can occur in the absence of insulin resistance, and that plasma TGs may have a detrimental effect on vascular reactivity.

A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelin

“…HOMA-IR is one of the most important parameters for the estimation of insulin resistance, providing acceptable and reliable results in rats, mice and humans (24). In the literature regarding HOMA-IR, we found studies with results similar to ours (25), and others with opposite outcomes (22). …”

Pre-treatment with a DPP-4 Inhibitor is Infarct Sparing in Hearts from Obese, Pre-diabetic Rats

“…As hearts from the DIO animals are bigger, they have a higher baseline coronary flow than hearts from control animals. The model that we used, has previously been demonstrated to suffer from endothelial dysfunction, specifically an impairment in acetylcholine-induced vasorelaxation [31]. As coronary flow was not enhanced in hearts from the DIO animals it can be concluded that treatment with the DPP4 inhibitor could not alleviate this impairment.…”

Diet, obesity and endothelial dysfunction: of rats and men

“…The induction of obesity in the study by Naderali et al [1] did not appear to be related to insulin resistance, as measured using the homoeostasis model assessment (HOMA). This was a surprising finding, given that obesity was found to be associated with arterial vascular resistance.…”

“…This was a surprising finding, given that obesity was found to be associated with arterial vascular resistance. As recognized by the authors [1], insulinmediated arterial vasodilation operates via the release of NO. In humans, endothelial dysfunction has accordingly been correlated with insulin resistance estimated by the hyperinsulinaemic euglycaemic clamp [7].…”

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We read with interest in a previous issue of Clinical Science the paper by Naderali et al [1] concerning the nutritional induction of obesity in Wistar rats and the subsequent relationship between hypertriacylglycerolaemia and endothelial dysfunction. Acknowledging the difficulties of drawing inferences for humans from studies carried out in experimental animals, the paper raises several interesting issues concerning the mechanisms whereby an unfavourable diet may lead to obesity and vascular disease.

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