Sex-specific differences in the development of acute alcohol-induced liver steatosis in mice

Alcohol Alcohol. 2013 Nov-Dec;48(6):648-56. doi: 10.1093/alcalc/agt138. Epub 2013 Aug 21.


Aims: Results of several animal studies suggest that similar to humans, female rodents are more susceptible to chronic alcohol-induced liver disease (ALD). The aim of the present study was to determine whether female mice are more susceptible to acute alcohol-induced steatosis than male mice and to investigate possible mechanisms involved.

Methods: Male and female C57BL/6J mice received one single dose of ethanol (6 g/kg bodyweight) or isocaloric maltose-dextrin solution intragastrically. Plasma alcohol concentration, markers of hepatic steatosis, activation of the TLR-4 signaling cascade and triglyceride export as well as lipid peroxidation and of iron metabolism were measured 12 h after acute alcohol intake.

Results: In male and female ethanol-treated mice, plasma alcohol concentrations were still markedly increased 12 h after the alcohol challenge, which was associated with a significant accumulation of lipids in the liver and increase of transaminases in plasma; however, lipid accumulation was ∼3-fold higher in females in comparison with male animals. Expression of MyD88 was only found to be significantly induced in livers of female alcohol-exposed mice, whereas protein levels of ApoB were found to be significantly lower only in livers of female mice exposed to ethanol. Levels of 4-HNE protein adducts and ferritin were induced in livers of male and female ethanol-treated mice.

Conclusion: Taken together, these data suggest that female mice are also more susceptible to acute alcohol-induced liver steatosis and that this involves an increased activation of TLR-4-dependent signaling pathways in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / metabolism
  • Aldehydes / metabolism
  • Animals
  • Aspartate Aminotransferases / metabolism
  • Carrier Proteins / metabolism
  • Central Nervous System Depressants / blood
  • Ethanol / blood
  • Fatty Liver, Alcoholic / pathology*
  • Female
  • Intestinal Absorption / physiology
  • Iron / metabolism
  • Kupffer Cells / metabolism
  • Lipid Metabolism / drug effects
  • Liver Function Tests
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Occludin / metabolism
  • Permeability
  • RNA / biosynthesis
  • RNA / isolation & purification
  • Real-Time Polymerase Chain Reaction
  • Sex Characteristics
  • Tumor Necrosis Factor-alpha / metabolism


  • Aldehydes
  • Carrier Proteins
  • Central Nervous System Depressants
  • Occludin
  • Tumor Necrosis Factor-alpha
  • microsomal triglyceride transfer protein
  • Ethanol
  • RNA
  • Iron
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • 4-hydroxy-2-nonenal