Recently, we demonstrated a role for ceramide-mediated neurodegeneration in a model of diet-induced obesity with T2DM [45], and showed that in vitro ceramide exposure causes neurodegeneration with impairments in neuronal viability, energy metabolism and insulin/IGF signaling mechanisms [83], consistent with previous reports [45,83,85,88-90,108-110]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.