Leptin is one of the key molecules in maintaining energy homeostasis. Although genetically leptin-deficient Lepob/Lepob mice have greatly contributed to elucidating leptin physiology, the use of more than one species can improve the accuracy of analysis results. Using the N-ethyl-N-nitrosourea mutagenesis method, we generated a leptindeficient Lepmkyo/Lepmkyo rat that had a nonsense mutation (Q92X) in leptin gene. Lepmkyo/Lepmkyo rats showed obese phenotypes including severe fatty liver, which were comparable to Lepob/Lepob mice. To identify genes that respond to leptin in the liver, we performed microarray analysis with Lepmkyo/Lepmkyo rats and Lepob/Lepob mice. We sorted out genes whose expression levels in the liver of Lepmkyo/Lepmkyo rats were changed from wild-type (WT) rats and were reversed toward WT rats by leptin administration. In this analysis, livers were sampled for 6 h, a relatively short time after leptin administration to avoid the secondary effect of metabolic changes such as improvement of fatty liver. We did the same procedure in Lepob/Lepob mice and selected genes whose expression patterns were common in rat and mouse. We verified their gene expressions by real-time quantitative PCR. Finally, we identified eight genes that primarily respond to leptin in the liver commonly in rat and mouse. These genes might be important for the effect of leptin in the liver. [ABSTRACT FROM AUTHOR]