Fenretinide is a synthetic retinoid that is being tested in clinical trials for the treatment of
breast cancer and insulin resistance, but its mechanism of action has been elusive. Recent
in vitro data indicate that fenretinide inhibits dihydroceramide desaturase, an enzyme
involved in the biosynthesis of lipotoxic ceramides that antagonize insulin action. Because of
this finding, we assessed whether fenretinide could improve insulin sensitivity and glucose
homeostasis in vitro and in vivo by controlling ceramide production. The effect of fenretinide …