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

Terrence Donohue, Natalia A Osna, Casey S. Trambly, Nash P. Whitaker, Paul G Thomes, Sandra L. Todero, John S Davis

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 8weeks. Results: Compared with controls, acute EtOH-treated mice showed a rapid, transient elevation in serum endotoxin beginning 30minutes after treatment. One hour postgavage, livers from EtOH-treated mice exhibited a robust elevation of both Egr-1 mRNA and protein. By 3hours 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.

Original languageEnglish (US)
Pages (from-to)759-767
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume36
Issue number5
DOIs
StatePublished - May 1 2012

Fingerprint

Liver
Ethanol
Fatty Liver
Growth
Endotoxins
Early Growth Response Protein 1
Wounds and Injuries
Triglycerides
Binge Drinking
Maltose
Therapeutics
Serum
Intubation
Nutrition
Lipid Peroxidation
Metabolism
Stomach
Transcription Factors
Phosphates
Animals

Keywords

  • Alcoholic Liver Injury
  • Fatty Liver
  • Glutathione
  • Oxidant Stress
  • Transcription Factors

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Early Growth Response-1 Contributes to Steatosis Development After Acute Ethanol Administration. / Donohue, Terrence; Osna, Natalia A; Trambly, Casey S.; Whitaker, Nash P.; Thomes, Paul G; Todero, Sandra L.; Davis, John S.

In: Alcoholism: Clinical and Experimental Research, Vol. 36, No. 5, 01.05.2012, p. 759-767.

Research output: Contribution to journalArticle

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AU - Donohue, Terrence

AU - Osna, Natalia A

AU - Trambly, Casey S.

AU - Whitaker, Nash P.

AU - Thomes, Paul G

AU - Todero, Sandra L.

AU - Davis, John S

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N2 - 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 8weeks. Results: Compared with controls, acute EtOH-treated mice showed a rapid, transient elevation in serum endotoxin beginning 30minutes after treatment. One hour postgavage, livers from EtOH-treated mice exhibited a robust elevation of both Egr-1 mRNA and protein. By 3hours 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.

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