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Early Growth Response-1 Contributes to Steatosis Development After Acute Ethanol Administration
Version of Record online: 5 DEC 2011
Copyright © 2011 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 36, Issue 5, pages 759–767, May 2012
How to Cite
Donohue, T. M., Osna, N. A., Trambly, C. S., Whitaker, N. P., Thomes, P. G., Todero, S. L. and Davis, J. S. (2012), Early Growth Response-1 Contributes to Steatosis Development After Acute Ethanol Administration. Alcoholism: Clinical and Experimental Research, 36: 759–767. doi: 10.1111/j.1530-0277.2011.01681.x
- Issue online: 30 APR 2012
- Version of Record online: 5 DEC 2011
- Received for publication May 19, 2011; accepted September 2, 2011.
- Alcoholic Liver Injury;
- Fatty Liver;
- Oxidant Stress;
- Transcription Factors;
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 (EtOH) administration. Here, we determined the extent to which Egr-1 is involved in fatty liver development in mice subjected to acute EtOH administration.
Methods: In acute studies, we treated both wild-type and Egr-1 null mice with either EtOH 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 EtOH or isocaloric maltose-dextrin for 7 to 8 weeks.
Results: Compared with controls, acute EtOH-treated mice showed a rapid, transient elevation in serum endotoxin beginning 30 minutes after treatment. One hour postgavage, livers from EtOH-treated mice exhibited a robust elevation of both Egr-1 mRNA and protein. By 3 hours postgavage, liver triglyceride increased in EtOH-treated mice as did lipid peroxidation. Acute EtOH treatment of Egr-1-null mice showed no Egr-1 expression, but these animals still developed elevated triglycerides, although significantly lower than EtOH-fed wild-type littermates. Despite showing decreased fatty liver, EtOH-treated Egr-1 null mice exhibited greater liver injury. After chronic EtOH feeding, steatosis and liver enlargement were clearly evident, but there was no indication of elevated endotoxin. Egr-1 levels in EtOH-fed mice were equal to those of pair-fed controls.
Conclusions: Acute EtOH administration induced the synthesis of Egr-1 in mouse liver. However, despite its robust increase, the transcription factor had a smaller, albeit significant, function in steatosis development after acute EtOH treatment. We propose that the rise in Egr-1 after acute EtOH is an hepatoprotective adaptation to acute liver injury from binge drinking that is triggered by EtOH metabolism and elevated levels of endotoxin.