Since the role of SphK1/S1P and S1P receptors in obesity is still not well understood, we investigated the role of S1P receptors and the effect of fingolimod on the expression of several genes encoding sphingosine kinase 1, S1P receptors, ADAM10, BACE1, PSEN2, GSK3β, SIRT1, proapoptotic Bax, and proinflammatory cytokines in the brains of obese mice. This evidence concerns the gene SIRT1 and obesity due to melanocortin 4 receptor deficiency.