We demonstrate that genetic manipulations that cause direct ceramide accumulation induce obesity by two distinct mechanisms: 1) Dihydroceramide (C14:0) and ceramide diene (C14:2) accumulation lowered fat store mobilization by reducing adipokinetic hormone- producing cell functionality and 2) decreasing the S1P: ceramide (C14:1) ratio suppressed postprandial satiety via the hindgut-specific neuropeptide like receptor dNepYr. This evidence concerns the gene MBTPS1 and obesity due to melanocortin 4 receptor deficiency.