Thus, it is conceivable that CerS6-derived ceramide-dependent effects on ER/mitochondrial dynamics during the development of diet-induced obesity lead to impaired ER/mitochondrial Ca2+ homeostasis, which alters POMC neuron intrinsic activity, ultimately changing feeding behavior and impairing metabolic control. Here, POMC is linked to obesity due to melanocortin 4 receptor deficiency.