Combination of alcohol and fructose exacerbates metabolic imbalance in terms of hepatic damage, dyslipidemia, and insulin resistance in rats

PLoS One. 2014 Aug 7;9(8):e104220. doi: 10.1371/journal.pone.0104220. eCollection 2014.


Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (≤3rd week), whereas fructose-fed animals had higher LW than controls (P<0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide:insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial β-oxidation of fatty acids (Cpt1α and Ppar-α expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and insulin resistance-accompanied liver damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholesterol, HDL / blood
  • Dyslipidemias* / blood
  • Dyslipidemias* / chemically induced
  • Dyslipidemias* / pathology
  • Ethanol / adverse effects*
  • Ethanol / pharmacology
  • Fructose / adverse effects*
  • Fructose / pharmacology
  • Insulin Resistance*
  • Liver* / injuries
  • Liver* / metabolism
  • Liver* / pathology
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / chemically induced
  • Metabolic Syndrome / pathology
  • Mitochondria, Liver* / metabolism
  • Mitochondria, Liver* / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Triglycerides / blood


  • Cholesterol, HDL
  • Triglycerides
  • Fructose
  • Ethanol

Grants and funding

This study was financed by UMG budget resources. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.