Inhibitors of SPT, CerS, and Des1, that all suppress sphingolipid synthesis by inhibiting different steps in the de novo pathway, have demonstrated beneficial effects in improving hepatic and nonhepatic manifestations of NAFLD (i.e., the excessive lipid droplets accumulation in steatosis, whole body IR, hyperglycemia, and hypertriglyceridemia) in animal models (12). This evidence concerns the gene AGXT and metabolic dysfunction-associated steatotic liver disease.