Hammarstedt A, Smith U
The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Diabetologia. 2003 Jan;46(1):48-52. doi: 10.1007/s00125-002-1002-7. Epub 2003 Jan 3.
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.
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.
L6 muscle cells showed a low expression of PPARgamma 1, no expression of PPARgamma 2, 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.
目的/假设：噻唑烷二酮类（TZD）在脂肪组织中的多种作用已得到证实，但对骨骼肌的作用却知之甚少。我们研究了TZD和过氧化物酶体增殖物激活受体α（PPARα）配体对L6肌肉细胞中不同基因表达的影响。
将L6肌肉细胞暴露于PPARα和PPARγ配体不同时间。采用实时聚合酶链反应（PCR）检测信号分子胰岛素受体底物-1（IRS-1）、胰岛素受体底物-2（IRS-2）、蛋白激酶B/蛋白激酶B（PKB/Akt）、转录因子C/EBPα、解偶联蛋白UCP-2和脂肪细胞标志物aP2的基因表达。为直接检测C/EBPα对基因表达的影响，我们还用该基因转染了L6细胞。
L6肌肉细胞PPARγ1表达较低，PPARγ2无表达，TZD对此无改变。PPARγ配体而非PPARα配体可迅速增加C/EBPα的表达，而UCP-2尤其是IRS-1基因在12 - 24小时缓慢激活。相反，PKB/Akt和IRS-2的表达均未改变。用C/EBPα转染并未增加IRS-1的表达。未发现TZD使肌肉转分化为脂肪细胞表型的证据，因为未检测到aP2表达。
结论/解读：TZD可增加L6肌肉细胞中IRS-1、UCP2和C/EBPα的表达。TZD激活C/EBPα可能是必要的，但不足以解释IRS-1表达的增加。
