The assessment of the effects of resveratrol on vascular and biochemical parameters within a model of metabolic syndrome induced by aging and fructose in male and female rats

Thesis Type: Doctorate

Institution Of The Thesis: Gazi Üniversitesi, Sağlık Bilimleri Enstitüsü, Turkey

Approval Date: 2013


Consultant: FATMA AKAR


The recent dramatic increase in the frequencies of obesity and metabolic syndrome can be substantially attributed to the consumption of fast foods and beverages that contain high amounts of fructose. Being naturally found in several fruits, resveratrol is a phytoalexin with a polyphenolic structure which exerts anti-oxidant effects on especially cardiovascular system. Despite the previously conducted studies, the influence of resveratrol intake over the long-term high-fructose diet and metabolic syndrome has not yet been clarified. The present study aims to investigate the effects of resveratrol treatment on the vascular, metabolic and histological alterations in relation with metabolic syndrome model which is induced by fructose consumption. In this study, both male and female Wistar rats have been fed with chow pellet containing 0.05% resveratrol and drinking water consisting of 10% fructose during 24 weeks. Afterwards, biochemical parameters were assessed in the blood and liver specimens of the recruited rats. Contraction response to phenylephrine (10-9-10-4M) as well as the relaxation responses to insulin (10-9-3×10-6M) and acetylcholine with L-NOARG (10-4M) and without L-NOARG (10-9-10-4M) were evaluated in thoracic aorta tissue. Moreover, IRS-1, eNOS, iNOS protein and mRNA concentrations were detected in both hepatic and aortic tissues by Western blotting and real-time polymerase chain reaction. In addition, liver tissue specimens were evaluated histopathologically. This study shows that the consumption of high fructose diet causes an increase in plasma glucose, insulin, triglyceride and VLDL concentrations as well as hepatic triglyceride levels and resveratrol treatment significantly decreases the aforementioned values in both male and female rats. High fructose diet also results in decreased HDL concentrations which are increased by resveratrol treatment in both male and female rats. Resveratrol treatment has also improved the attenuation in relaxation responses which are mediated by vascular endothelium-dependent acetylcholine and insulin throughout consumption of high fructose diet. What is more, resveratrol treatment supress the phenylephrine-mediated contraction response which is induced by high fructose intake. On the contrary, there were no alterations in acetylcholine-mediated relaxation responses within the existence of L-NOARG (10-4M). Resveratrol supplementation is found to decrease the abdominal circumference and treat hepatic hyperemia and degeneration findings in both male and female rats. Moreover, resveratrol treatment significantly increases the prominent decrease in eNOS protein and mRNA concentrations of aortic and hepatic tissues in response to high fructose diet. In addition, resveratrol treatment significantly decreases the dramatic increase in iNOS protein and mRNA concentrations of aortic tissue which is triggered by high fructose intake. Although the concentrations of IRS-1 protein and mRNA concentrations in aorta tissues are not altered by high fructose diet, these values are partially increased by resveratrol treatment. Sex differences in plasma triglyceride, VLDL and HDL concentrations shown higher level at fructose-fed female rats compared to male rats. Venous blood glucose levels observed no difference between male and female rats, but arterial blood glucose levels were higher levels of male rats. Tissue weights and plasma insulin levels, no differences were observed in terms of male and female rats. Fructose-fed male rats compared to female rats decreased the effectiveness of phenylephrine, but no significant difference relaxant responses to acetylcholine and insulin are shown not occur. Rats aorta male rats compared to the expression of iNOS protein was shown to be higher level at fructose-fed female rats compared to male rats. eNOS and IRS-1 levels were not observed any difference in the sex-linked. The findings of the present study show that resveratrol supplementation can improve vascular dysfunction and metabolic disorders which are induced by high fructose diet. Theferore, it can be suggested that resveratrol supplementation may have benefit in individuals who are on high fructose diet.