In our lab, the mice were initially fed the control liquid dextrose diet (Bio-Serv, Frenchtown, NJ) for 3 days to acclimate them to the liquid diet. Afterward, the mice were fed the liquid ethanol diet (Bio-Serv, Frenchtown, NJ) as described by Lieber and DeCarli (Lieber and DeCarli, 1994). The content of ethanol was gradually increased from 10% of total calories to 20%, 25%, 30%, and finally 35% of total calories (about 6.2% [vol/vol]). The liquid dextrose diet were fed on an iso-energetic basis as a control. The ethanol-fed mice had access to their rations ad libitum. The total feeding duration was 3 weeks (21 days). The amount of food consumed by the different genetically mutated mice used in this study was approximately the same. Some mice were daily injected mouse recombinant FGF21 (rFGF21, purchased from Creative Biomart, Shirley, NY, USA) subcutaneously at 0.25 mg/kg body weight. The mice were fasted for 6 h and then sacrificed by cervical dislocation after blood was collected via the retro-orbital venous sinus under anesthesia by inhalation of isoflurane. The livers were rapidly excised into