In this study, using transcriptional profiling of key tissues, we aimed to identify genetic mechanisms differing between control pigs and pigs that have been under selection for low residual feed intake (RFI) for three generations. A further aim was to determine the pathways responding to feed restriction within these lines and any line x treatment interactions resulting in gene expression differences. Preliminary results indicate that 2,809 genes in fat (p<0.04, q<0.2) and 61 genes in liver (p<0.001, q<0.2) showed differential expression in response to feed restriction. Also, 1,247 genes (p<0.02, q<0.2) showed differential expression between low RFI and control pigs and 38 genes (p<0.001, q<0.2) showed a line x feed interaction in liver. In addition, we measured the concentration of some of the important feed intake regulators in the blood such as leptin, triglyceride, and glucose. We found that the average blood leptin level to be significantly higher in the control ad libitum (CA) pigs than the control restricted (CR) group. Interestingly, the selected line of pigs on both restricted (SR) and ad libitum (SA) feed had similar blood leptin levels as found in the CR group pigs. Serum glucose levels were higher in CR than CA, however, we observed an opposite trend in the selected group. Combined with the transcriptional profiling results, blood hormone parameters may help us understand potential pathways that control FI and FE in pigs.