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

Drug Res (Stuttg). 2017 Feb;67(2):103-110. doi: 10.1055/s-0042-118386. Epub 2016 Nov 7.

Abstract

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.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Biomarkers / blood
  • Body Weight / drug effects
  • Diet, Carbohydrate Loading / adverse effects*
  • Female
  • Fructose / administration & dosage
  • Fructose / adverse effects*
  • High Fructose Corn Syrup / administration & dosage
  • High Fructose Corn Syrup / adverse effects
  • Insulin / metabolism
  • Insulin Receptor Substrate Proteins / metabolism
  • Interleukin-1beta / metabolism
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Nitric Oxide Synthase Type III / metabolism*
  • Non-alcoholic Fatty Liver Disease / chemically induced*
  • Non-alcoholic Fatty Liver Disease / enzymology*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Rats
  • Rats, Wistar
  • Receptor, Insulin / metabolism
  • Resveratrol
  • Signal Transduction
  • Stilbenes / administration & dosage
  • Stilbenes / pharmacology*
  • Triglycerides / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Biomarkers
  • High Fructose Corn Syrup
  • IL1B protein, rat
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Interleukin-1beta
  • Irs1 protein, rat
  • Stilbenes
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Fructose
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Receptor, Insulin
  • Resveratrol