Resveratrol inhibits Des1 and protects insulin signaling.
A, similar to fenretinide treatment, the addition of 20 μm RSV improved insulin signaling (100 nm, 10 min) in C2C12 myotubes exposed to 0.75 mm PA for 16 h. pAkt, phosphorylated Akt; Sirt1 KO, Sirt1 knock-out. C and D, RSV significantly reduced ceramides and increased dihydroceramides when added to PA-containing medium in comparison with PA alone. A, B, and E, to confirm that these effects occurred independently of Sirt1, similar to Sirt1 inhibition with nicotinamide (NAM) (A), Sirt1 ablation with shRNA (B) had no effect on RSV-mediated improvements in insulin signaling (E). *, p < 0.05 for treatment versus BSA. +, p < 0.05 for PA+RSV versus PA (n = 3–6).