title: Sex-specific differences in the development of acute alcohol-induced liver steatosis in mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Corresponding author: Department of Nutritional Sciences, Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Dornburger Str. 25, 07743 Jena, Germany. ina.bergheim@uni-jena.de.
authors: Sabine
authors: S
authors: Wagnerberger
authors: Lena
authors: L
authors: Fiederlein
authors: Giridhar
authors: G
authors: Kanuri
authors: Carolin
authors: C
authors: Stahl
authors: Gunda
authors: G
authors: Millonig
authors: Sebastian
authors: S
authors: Mueller
authors: Stephan C
authors: SC
authors: Bischoff
authors: Ina
authors: I
authors: Bergheim
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000097:blood; D000431:Ethanol / Q000097:blood; D005235:Fatty Liver, Alcoholic / Q000473:pathology*; D005260:Female; D007408:Intestinal Absorption / Q000502:physiology; D007501:Iron / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D062793:Occludin / Q000378:metabolism; D010539:Permeability; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D012727:Sex Characteristics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000447:Aldehydes; D002352:Carrier Proteins; D002492:Central Nervous System Depressants; D062793:Occludin; D014409:Tumor Necrosis Factor-alpha; C106092:microsomal triglyceride transfer protein; D000431:Ethanol; D012313:RNA; D007501:Iron; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C027576:4-hydroxy-2-nonenal