Long-Term Dietary Fructose Causes Gender-Different Metabolic and Vascular Dysfunction in Rats: Modulatory Effects of Resveratrol.
OBJECTIVE
There is limited knowledge on the gender differences in the effects of dietary fructose. In the current study, we investigated whether long-term fructose intake impacts metabolic parameters and vascular reactivity differently between male and female rats. Moreover, we tested whether resveratrol has a gender-specific effectiveness on the alterations.


METHODS
Male and female rats were divided into four groups as control; resveratrol; fructose and resveratrol plus fructose. Fructose was given to the rats as 10% solution in drinking water for 24 weeks. All rats were fed with the standard diet with or without resveratrol.


RESULTS
High-fructose diet increased plasma insulin, triglyceride and VLDL levels as well as omental weights in both genders. Long-term dietary fructose causes marked increase in body weight of males, but not females. Dietary fructose impaired endothelial relaxation to acetylcholine and intensified contraction to phenylephrine in the aortas of male and female rats, but differently it also reduced insulin-induced vasodilation in aortas of female rats. These changes were associated with decreased expression levels of endothelial nitric oxide synthase (eNOS) mRNA and protein, but increased in inducible NOS (iNOS), in aortas of male and female rats. Dietary fructose suppressed expression levels of sirtuin 1 (SIRT1) and insulin receptor substrate-2 (IRS-2) mRNA in aortas from female rats. Resveratrol supplementation efficiently restored fructose-induced metabolic and vascular dysfunction in both genders probably by regulating eNOS and iNOS production. Moreover, the augmentations in SIRT1 and IRS-2 mRNA in females and IRS-1 mRNA in males may possibly contribute to the beneficial effects of resveratrol as well.


CONCLUSIONS
Long-term fructose intake may differently affect metabolic and vascular function between male and female rats, which are modified by resveratrol.
Mehmet Bilgehan
MB
Pektaş
Gökhan
G
Sadi
Fatma
F
Akar
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D004032:Diet; D005260:Female; D005632:Fructose / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010656:Phenylephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D012737:Sex Factors; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D000975:Antioxidants; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526299:Irs2 protein, rat; D008079:Lipoproteins, VLDL; D013267:Stilbenes; D014280:Triglycerides; D010656:Phenylephrine; D005632:Fructose; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D056564:Sirtuin 1; D000109:Acetylcholine; D000077185:Resveratrol