Indeed, inhibition of serine palmitoyltransferase (SPT), the rate-limiting step in ceramide biosynthesis, or deletion of its subunits Sptlc1 or Sptlc2 in obese mice limits the formation of these obesogenic sphingolipids and consequently reduces diet-induced obesity, improves glucose tolerance and insulin resistance, preventing the progression to NASH [[12], [13], [14]]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.