SPHK2 and obesity due to melanocortin 4 receptor deficiency: Notably, SphK2−/− mice are protected from diet-induced obesity and develop a lean phenotype and improved glucose tolerance [162] and are characterized by a two-fold increase of S1P in plasma, suggesting that the inhibition of SphK2 contributes to the maintenance of high levels of S1P and may be potentially positive in the treatment of obesity.