Acute fenretinide injection selectively inhibits ceramide accumulation. HFD-fed male C57Bl/6 mice received 10 mg/kg of FEN via intraperitoneal injection 12 h prior to sacrifice. A and C, ceramides tended to decrease in both the soleus (Sol.) and the liver (Hep.) (A and C), but did not reach significance. B and D, however, FEN injection induced a roughly 6-fold increase in dihydroceramides in the soleus (B) and a 2-fold increase in the liver (D). *, p < 0.05 for treatment versus PBS injection (n = 5).