This was likely due to the fact that MC4RF51L mice had increased leptinergic signaling (see Table 1), leading to greater melanocortinergic input to the PVN, which would be expected to increase CREB phosphorylation if MC4R/Gsα/cAMP signaling is intact in the mutant receptor — although other mechanisms associated with obesity may also be involved. This evidence concerns the gene GNAS and obesity due to melanocortin 4 receptor deficiency.