Among the two forms of SphK (SphK1 and SphK2) [39], SphK1 expression is increased in insulin sensitive tissues but also in islets of Langerhans from mice under high fat diet (HFD) and in T2D patients [40], suggesting that this enzyme is involved in the onset of T2D associated with obesity. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.