Currently the strongest evidence for ceramide-specific control over the mitochondrial fission process comes from the study by Hammerschmidt et al. in which the ablation of CerS6 in a mouse model of HFD-induced insulin resistance facilitated a successful reversal of the fragmentation of hepatic mitochondrial network, rescued the insulin-sensitive phenotype and prevented HFD-induced obesity (64). Here, CERS6 is linked to obesity due to melanocortin 4 receptor deficiency.