Dietary Fructose-Induced Hepatic Injury in Male and Female Rats: Influence of Resveratrol.

Purpose: Relatively little is known about gender-dependent susceptibility to hepatic injury induced by nutritional factors. In the current study, we investigated dietary fructose-induced hepatic degeneration and roles of endothelial nitric oxide synthase (eNOS), insulin receptor (IRβ) and substrate-1 (IRS-1) expressions in association with inflammatory markers in male and female rats. Moreover, we examined potential effect of resveratrol on fructose-induced changes. Methods: Male and female rats were divided into 4 groups as control, resveratrol, fructose and resveratrol plus fructose. All rats were fed with a standard diet with or without resveratrol (500 mg/kg). Fructose was given as 10% in drinking waterfor 24 weeks. Results: Long-term dietary fructose caused parenchymal degeneration and hyperemia in association with impaired eNOS mRNA/protein expressions in liver of male and female rats. This dietary intervention also led to increases in hepatic triglyceride content, TNFα and IL-1β levels in both genders. Gender-related differences to consequence of fructose consumption were not obvious. Resveratrol supplementation markedly attenuated hepatic degeneration, hyperemia and triglyceride content in association with reduced TNFα and IL-1β levels, but enhanced IRβ mRNA and IRS-1 protein, in male and female rats upon fructose feeding. Conclusion: Long-term dietary fructose causes hepatic degeneration possibly via a decrease in eNOS, but increase in TNFα and IL-1β, in both genders. Resveratrol supplementation improved fructose-induced hepatic injury.