Palmitate increases transcription of multiple enzymes of de novo sphingolipid synthesis. C2C12 myotubes were treated with palmitate (PA; 16 h, 0.75 mM) in the absence (PA) or presence of AICAR (PA+AIC; 2 mM). Levels of serinepalmitoyl transferase 2 (SPT2) and ceramide synthase 2 and 6 (CerS 2 and 6) were elevated with PA, but only SPT2 was significantly affected by inclusion of AICAR. Moreover, addition of Compound C (20 μM) caused a robust increase in SPT2 and, to a lesser degree, CerS6 transcript levels. SPT1-2: serine palmitoyltransferase 1–2; CerS 1–6: ceramide synthase 1–6; Des1: dihydroceramide desaturase 1; GCS: glucosylceramide synthase. *p<0.05 for PA vs BSA. +p<0.05 for PA+AIC vs PA. §p<0.05 for PA+AIC+CC vs. PA+AIC (n=4).