Early Growth Response-1 Contributes to Steatosis Development After Acute Ethanol Administration

Background—Previous work demonstrated that the transcription factor, early growth response-1 (Egr-1) participates in the development of steatosis (fatty liver) after chronic ethanol administration. Here, we determined the extent to which Egr-1 is involved in fatty liver development in mice subjected to acute ethanol administration. Methods—In acute studies, we treated both wild type and Egr-1 null mice with either ethanol or phosphate-buffered saline (PBS) by gastric intubation. At various times after treatment, we harvested sera and livers and quantified endotoxin, indices of liver injury, steatosis, and hepatic Egr-1 content. In chronic studies, groups of mice were fed liquid diets containing either ethanol or isocaloric maltose-dextrin for 7-8 weeks. Results—Compared with controls, acute ethanol-treated mice showed a rapid, transient elevation in serum endotoxin beginning 30 minutes after treatment. One hour post-gavage, livers from ethanol-treated mice exhibited a robust elevation of both Egr-1 mRNA and protein. By three hours post-gavage, liver triglyceride increased in ethanol-treated mice as did lipid peroxidation. Acute ethanol treatment of Egr-1-null mice showed no Egr-1 expression, but these animals stil