P053

An inhibitor of CerS1 (IC50s = 0.54 and 0.46 µM for human and mouse CerS1, respectively); selective for CerS1 over CerS2, CerS4, CerS5, and CerS6 (IC50s = 28.6, 17.2, 7.2, and 11.4 µM, respectively); lowers levels of C18 ceramide, C18 galactosylceramide, and C18:0 and 18:1 sphingomyelin species in HEK293 cells at 30-300 nM; decreases endogenous C18:1/18:0 and C18:2/18:0 ceramide levels in mouse skeletal muscle at 5 mg/kg; increases fatty acid oxidation in mouse skeletal muscle and inhibits triglyceride synthesis and increases in white adipose mass in a model of high-fat diet-induced obesity but does not affect insulin resistance