A. Protein levels of SIRT1 are measured in AML12 hepatocytes and in livers of wild-type (WT) mice and SIRT1 liver-specific knockout (SIRT1 LKO) mice under conditions of normal and ethanol exposure. B. Hepatocyte-specific deletion of SIRT1 downregulates DEPTOR and enhances mTORC1 activation in mice after chronic-binge ethanol feeding. C. Genetic ablation of SIRT1 in the liver increases the susceptibility to alcohol-induced fatty liver. D. Hepatic SIRT1 deficiency exacerbates alcohol-mediated abnormalities of lipid metabolism in mice. E–F. Hepatic SIRT1 loss aggravates alcohol-induced inflammation, apoptosis, and liver injury. The data are presented as the mean ± SEM, n = 4–8. *P < 0.05, vs. pair-fed WT mice; #P < 0.05, vs. ethanol-fed WT mice.