Previous studies on sphingolipid contributions to metabolic dysfunction showed that the depletion of ceramides, particularly C16:0 and C18:0 ceramides, can prevent or even reverse the development of hepatic steatosis, as well as improve systemic glucose tolerance and insulin sensitivity in adult mice with HFD-induced obesity (74, 78). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.