Molecular mechanism of SHP/REV-ERBalpha/CYP4A axis in mediating alcohol-induced livery injury

The molecular mechanisms of CYP4A in ALD pathogenesis has not been elucidated. In the current study, we found that hepatic Cyp4a10 and Cyp4a14 expression were significantly upregulated in WT, but not in Shp-/- mice fed with ethanol. SHP knockout and wild type mice were fed 5% Lieber-DeCarli ethanol liquid diet (Bio-Serv; #F1258SP) or maltose control for 10 days followed by a binge of alcohol (5g/kg body weight) or isocaloric maltose dextrin (9g/kg body weight) at 9am on day 11. Liver samples were collected from groups of 3 control or ethanol fed mice serially post gavage at 6pm, 12am, 6am or 12pm over a 24-hour period.