Large-scale gene profiling of the liver in a mouse model of chronic, intragastric ethanol infusion

J Hepatol. 2004 Feb;40(2):219-27. doi: 10.1016/j.jhep.2003.10.021.

Abstract

Background/aims: The mechanisms underlying alcohol-induced liver injury are not fully elucidated. An approach in this direction would consist of an all-inclusive assessment of gene expression in the liver. The purpose of this study was to perform a comprehensive analysis of gene expression in the livers of mice treated with ethanol by means of intragastric infusion.

Methods: An ethanol- or glucose-enriched liquid diet was fed to animals for 4 weeks via a long-term gastrostomy catheter. The animals were killed and plasma alanine:2-oxoglutarate aminotransferase (ALT) assay, liver histology and total RNA analysis by microarray gene technology were performed.

Results: Alcohol increased ALT, induced steatosis, necrosis and inflammation. A total of 12,423 genes were analyzed for expression out of which 4867 were expressed by the liver. Alcohol repressed expression of 11 genes, induced expression of 13 genes, and up- or down-regulated expression of 44 and 42 genes >2-fold, respectively. Gene expression analysis identified several genes that have not previously been tested for alcohol effects.

Conclusions: This study: (i) expands the knowledge of mechanism(s) of action of ethanol; (ii) indicates novel pathways of ethanol action on the liver, and (iii) illustrates the utility of microarray gene analysis in hepatology research.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Central Nervous System Depressants / blood
  • Central Nervous System Depressants / pharmacology
  • Chronic Disease
  • Disease Models, Animal
  • Ethanol / blood
  • Ethanol / pharmacology
  • Fatty Liver, Alcoholic / genetics*
  • Fatty Liver, Alcoholic / pathology
  • Fatty Liver, Alcoholic / physiopathology*
  • Liver / pathology
  • Liver / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Necrosis
  • Oligonucleotide Array Sequence Analysis*

Substances

  • Central Nervous System Depressants
  • Ethanol
  • Alanine Transaminase