High-fructose corn syrup-induced hepatic dysfunction in rats: improving effect of resveratrol

Eur J Nutr. 2015 Sep;54(6):895-904. doi: 10.1007/s00394-014-0765-1. Epub 2014 Sep 11.


Purpose: The increased consumption of high-fructose corn syrup (HFCS) may contribute to the worldwide epidemic of fatty liver. In this study, we have investigated whether HFCS intake (20% beverages) influences lipid synthesis and accumulation in conjunction with insulin receptor substrate-1/2 (IRS-1; IRS-2), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1) and inducible NOS (iNOS) expressions in liver of rats. Resveratrol was tested for its potential efficacy on changes induced by HFCS.

Methods: Animals were randomly divided into four groups as control, resveratrol, HFCS and resveratrol plus HFCS (resveratrol + HFCS). HFCS was given as 20% solutions in drinking water. Feeding of all rats was maintained by a standard diet that enriched with or without resveratrol for 12 weeks.

Results: Dietary HFCS increased triglyceride content and caused mild microvesicular steatosis in association with up-regulation of fatty acid synthase and sterol regulatory element binding protein (SREBP)-1c in liver of rats. Moreover, HFCS feeding impaired hepatic expression levels of IRS-1, eNOS and SIRT1 mRNA/proteins, but did not change iNOS level. Resveratrol promoted IRS, eNOS and SIRT1, whereas suppressed SREBP-1c expression in rats fed with HFCS.

Conclusions: Resveratrol supplementation considerably restored hepatic changes induced by HFCS. The improvement of hepatic insulin signaling and activation of SIRT1 by resveratrol may be associated with decreased triglyceride content and expression levels of the lipogenic genes of the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / etiology
  • Enzyme Activation / drug effects
  • Fatty Acid Synthase, Type I / genetics
  • Gene Expression / drug effects
  • High Fructose Corn Syrup / administration & dosage*
  • Insulin / metabolism
  • Insulin Receptor Substrate Proteins / analysis
  • Insulin Receptor Substrate Proteins / genetics
  • Liver / chemistry
  • Liver / enzymology
  • Liver / metabolism
  • Male
  • Nitric Oxide Synthase Type III / analysis
  • Nitric Oxide Synthase Type III / genetics
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Resveratrol
  • Signal Transduction / drug effects
  • Sirtuin 1 / analysis
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Stilbenes / administration & dosage*
  • Triglycerides / analysis


  • High Fructose Corn Syrup
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, rat
  • RNA, Messenger
  • Sterol Regulatory Element Binding Protein 1
  • Stilbenes
  • Triglycerides
  • Nitric Oxide Synthase Type III
  • Fatty Acid Synthase, Type I
  • Sirt1 protein, rat
  • Sirtuin 1
  • Resveratrol