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

作者：Terrence M. Donohue, Natalia A. Osna, Casey S. Trambly, Nash Whitaker, Paul G. Thomes, Sandra L. Todero, John S. Davis · 发表于：Alcoholism Clinical and Experimental Research · 年份：2011 · DOI：10.1111/j.1530-0277.2011.01681.x · 被引用次数：30 · 研究领域：Alcohol Consumption and Health Effects、Prenatal Substance Exposure Effects、Growth Hormone and Insulin-like Growth 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 evide...