English: □ Control; ▪ 0.5 mM Palmitate. Palmitate has no effect on insulin receptor phosphorylation, but Akt activation is impaired in cultured primary rat hepatocytes treated for 20 h with palmitate. (a) The insulin-stimulated insulin receptor phosphorylation to total insulin receptor ratio is not altered in hepatocytes treated with palmitate. (b) However, insulin-stimulated phosphorylation of Akt Ser473 is significantly inhibited by palmitate. This effect is conferred onto the Akt substrates FoxO1 (Ser256) (c) and Gsk3α (Ser21) (d) which both show decreased insulin-stimulated phosphorylation. Fold change is relative to no insulin. Phosphorylation levels of individual proteins were normalized to the total amounts of the respective proteins. Data are averages of western blot quantifications +/− std. error of the mean, n = 8. * indicates p<0.05 between groups. Representative western blots are shown.