Fig. 4.

Inhibition of the de novo pathway with fenretinide does not reverse palmitate-induced insulin resistance, but reduces palmitate-induced inflammation. L6 myotubes were pretreated with fenretinide (10 μM) for 30 min and then incubated with 0.5 mM PA in the presence of fenretinide for 18 h. A: Lipid species were measured using lipidomics as described in the Methods. B: Surface GLUT4 was measured as described in the Methods [n = 9; three-way ANOVA (insulin, PA, fenretinide)]. C, D. Expression of Ccl2 and Il6 after PA and fenretinide exposure was measured by qPCR [n = 7; two-way ANOVA (PA, fenretinide)]. ^#Overall significant effect of inhibitor (two-way ANOVA; P < 0.05). *Significant effect of PA over BSA control (two-way ANOVA; P < 0.05). ^§Significant effect of insulin over unstimulated control (P < 0.05). DHCer, dihydroceramide; HexCer, hexosylceramide; SPM, sphingomyelin; LacCer, lactosylceramide; FEN, fenretinide.