(A) Myristate, but not palmitate, treatment induced hypertrophy in cardiomyocytes. This was prevented by inhibition of de novo sphingolipid synthesis with myriocin. Results are shown as percentage increase over BSA. (B) Myristate, but not palmitate, strongly induces C14-ceramide production in cardiomyocytes. (C) CerS5 and CerS6 are primarily responsible for synthesis of C14-ceramide. (D) siRNA-mediated knockdown of CerS5 is sufficient to prevent induction of hypertrophy by myristate. Results are given as percentage increase over control siRNA treated with BSA. For all panels, results are presented as mean ± SEM. *P < 0.05 vs. BSA; ***P < 0.005 vs. control BSA; #P < 0.05 vs. palmitate; †P < 0.005 vs. myristate DMSO.