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

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...

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Other Authors: Wagnerberger, Sabine (Other) , Fiederlein, Lena (Other) , Stahl, Carolin (Other) , Millonig, Gunda (Other) , Mueller, Sebastian (Other) , Bischoff, Stephan C. (Other)
Format: Article (Journal)
Language:English
Published: 21 August 2013
In: Alcohol and alcoholism
Year: 2013, Volume: 48, Issue: 6, Pages: 648-656
ISSN:1464-3502
DOI:10.1093/alcalc/agt138
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/alcalc/agt138
Verlag, lizenzpflichtig, Volltext: https://academic.oup.com/alcalc/article/48/6/648/446221
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Author Notes:Sabine Wagnerberger, Lena Fiederlein, Giridhar Kanuri, Carolin Stahl, Gunda Millonig, Sebastian Mueller, Stephan C. Bischoff and Ina Bergheim

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520 |a 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. 
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