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Genetic Contribution to Alcoholic Steatohepatitis
Author(s) -
DeSantis David Andrew,
Pisano Sorana,
Millward Carrie A.,
Gornicka Aga,
Soda Pamela,
McMullen Megan R.,
Pritchard Michelle T.,
Nagy Laura E.,
Croniger Colleen M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1037.10
Subject(s) - steatosis , steatohepatitis , fatty liver , cyp2e1 , liver injury , medicine , endocrinology , alcohol dehydrogenase , cirrhosis , biology , alcoholic fatty liver , knockout mouse , ethanol metabolism , ethanol , gene , cytochrome p450 , genetics , biochemistry , metabolism , disease
Chronic excessive alcohol intake is associated with multiple liver defects ranging from mild fatty liver (steatosis) to advanced cirrhosis. The mechanism by which chronic ethanol intake causes fatty liver appears to be a complex and multifactorial process. To better understand the contribution of genetics we have studied the response to alcohol in two inbred strains of mice, C57BL/6J and A/J. These mice were fed alcohol using the Lieber De‐Carli high‐fat control and ethanol containing diet. The C57BL/6J mice develop steatosis while the A/J mice are protected. We analyzed the expression of the transcription factor CCAAT/enhancer binding protein â (C/EBPâ) that has been implicated in the development of fatty liver and required for expression of alcohol dehydrogenase gene (ADH). In both mouse strains C/EBP â gene expression was increased with alcohol consumption but in the A/J mice the liver inhibitor protein (LIP) was increased while the C57BL/6J mice had an increase of the liver‐enhanced activator protein (LAP). Markers of liver damage, alanine aminotransferase (ALT), and CYP2E1 were elevated in both C57BL/6J and A/J mice. This suggests that there is a genetic contribution for the development of steatosis and that the elevation of ALT levels is decoupled from development of steatosis in the A/J mice. Further analysis is necessary for better understanding the mechanism of liver injury during alcohol consumption.