BackgroundDifferent strains of rats have been used to study alcoholic liver disease (ALD) while the reason for selecting a particular rat strain was not apparent.PurposeThe aim of our study was to compare outbred (Wistar) and inbred (Fischer) strains to evaluate pathological, biochemical changes, and gene expression differences associated with ethanol-induced early hepatic steatosis.Study DesignMale Wistar and Fischer-344 rats were pair-fed for 6 weeks with or without 5% ethanol in Lieber-DeCarli liquid diet. Livers were analyzed for histological and lipid-related differences.ResultsHepatic midzonal steatosis was mainly found in Wistar rats while Fischer rats showed mostly pericentral steatosis. Increased hepatic steatosis in ethanol-fed Wistar rats is supported by increases in lipids with related genes and transcription factors involved in fatty acid and triglyceride synthesis.ConclusionOur data showed that Fischer rats are relatively less prone to ethanol-mediated steatosis with pericentral lipid deposition pattern in the liver which is similar to humans and show no trace level of lipid accumulation in pair-fed controls as observed in Wistar (outbred) strain. Therefore, Fischer rats are better suited for lipid studies in an early development of ALD.