title: Early growth response-1 contributes to steatosis development after acute ethanol administration.
abstract: 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.
authors.affiliation: Liver Study Unit, Nebraska-Western Iowa Health Care System, College of Medicine, University of Nebraska Medical Center, Omaha, USA. tdonohue@unmc.edu
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Donohue
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Osna
authors.forename: Casey S
authors.initials: CS
authors.lastname: Trambly
authors.forename: Nash P
authors.initials: NP
authors.lastname: Whitaker
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomes
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Todero
authors.forename: John S
authors.initials: JS
authors.lastname: Davis
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D004731:Endotoxins / Q000097:blood; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D005235:Fatty Liver, Alcoholic / Q000209:etiology* / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D002492:Central Nervous System Depressants; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D004731:Endotoxins; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D000410:Alanine Transaminase; D005978:Glutathione