The effect of leptin on liver alcohol dehydrogenase (ADH) was determined in male rats. Administration of one or three daily doses of leptin (1 mu g/g of body weight intraperitoneally) increased ADH activity. Leptin enhanced ADH synthesis without an effect on ADH degradation. Leptin did not change ADH mRNA, indicating that the effect of leptin in enhancing ADH occurs at the post-transcriptional level. Leptin increased eukaryotic initiation factor (eIF) 2 alpha, eIF2B activity, and the eIF4E-eIF4G complex, while it decreased the inhibitory complex of eIF4E with the eIF4E-binding protein-1 (4E-BP1). Leptin increased mammalian target of rapamycin (mTor) that phosphorylates 4E-BP1. In conclusion, leptin increases liver ADH activity and ADH protein due to an increase in synthesis which occurs at the post-transcriptional level. The effect of leptin in enhancing translational initiating factors may be of significance in the regulation not only of ADH but also of many other proteins. (c) 2005 Elsevier Inc. All rights reserved.