Thiazolidinediones (PPARγ ligands) increase IRS-1, UCP-2 and C/EBPα expression, but not transdifferentiation, in L6 muscle cells

Aims/hypothesis. Several effects of thiazolidinediones (TZD) have been shown in adipose tissue but very little is known about the effects in skeletal muscle. We examined the effects of TZD and PPARalpha ligands on the expression of different genes in L6 muscle cells. Methods. L6 muscle cells were exposed to PPARalpha and PPARgamma ligands for different times. The gene expression of the signalling molecules IRS-1, IRS-2, PKB/Akt, the transcription factor C/EBPalpha, the uncoupling protein UCP-2 and the adipocyte marker aP2 were measured with real-time PCR. To directly examine the effect of C/EBPalpha on gene expression, we also transfected L6 cells with this gene. Results. L6 muscle cells showed a low expression of PPARgamma1, no expression of PPARgamma2, and this was not changed by TZD. PPARgamma, but not PPARalpha, ligands rapidly increased the expression of C/EBPalpha while UCP-2 and in particular the IRS-1 gene was activated with a slow onset (12-24 h). In contrast, neither PKB/Akt nor IRS-2 expression were changed. Transfection with C/EBPalpha did not increase IRS-1 expression. There was no evidence of transdifferentiation of the muscle to an adipocyte phenotype by TZD since no aP2 expression was found. Conclusion/interpretation. TZD increase IRS-1, UCP2 and C/EBPalpha expression in L6 muscle cells. Activation of C/EBPalpha by TZD could be necessary but it is not sufficient to account for the increased IRS-1 expression.