Department of Human Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Mol Nutr Food Res. 2010 Dec;54(12):1763-72. doi: 10.1002/mnfr.201000103.
The capacity of skeletal muscle to contribute to glucose homeostasis depends on muscular insulin sensitivity. The expression of glucose transporter (GLUT)-4 is increased during myoblast differentiation, a process essential in maintenance of adult muscle. Therefore, processes that affect muscle differentiation may influence insulin dependent glucose homeostasis. Conjugated linoleic acids, and in particular trans-10, cis-12 CLA (t10, c12-CLA), are potent inducers of NF-kB in cultured skeletal myotubes, and NF-kB activation inhibits muscle differentiation. The aims of this study were to evaluate whether CLAs inhibit myogenic differentiation and lower GLUT4 mRNA expression and to address the involvement of NF-kB activation in potential effects of CLA on these processes.
Incubation of C2C12 cells with t10, c12-CLA blocked the formation of myotubes, which was accompanied by reduced expression of the muscle specific genes creatine kinase, myogenin, myosin heavy chain perinatal and myosin heavy chain IIB, as well as decreased GLUT4 mRNA levels. However, genetic blockade of NF-kB was not sufficient to restore reduced myosin heavy chain protein expression following t10, c12-CLA treatment. Surprisingly, in contrast to myotubes, t10, c12-CLA was not able to activate NF-kB transcriptional activity in myoblasts.
In conclusion, t10, c12-CLA inhibits myogenic differentiation and GLUT4 expression, independently from NF-kB activation.
骨骼肌对葡萄糖稳态的贡献能力取决于肌肉胰岛素敏感性。葡萄糖转运蛋白（GLUT）-4的表达在成肌细胞分化过程中增加，这是维持成人肌肉的重要过程。因此，影响肌肉分化的过程可能会影响胰岛素依赖的葡萄糖稳态。共轭亚油酸，特别是反式-10，顺式-12 共轭亚油酸（t10，c12-CLA），是培养的骨骼肌成肌细胞中 NF-kB 的有效诱导剂，NF-kB 的激活抑制肌肉分化。本研究的目的是评估 CLA 是否抑制成肌分化并降低 GLUT4 mRNA 表达，并探讨 NF-kB 激活在 CLA 对这些过程的潜在影响中的作用。
用 t10，c12-CLA 孵育 C2C12 细胞可阻断肌管的形成，同时伴随肌特异性基因肌酸激酶、成肌生成素、肌球蛋白重链围产期和肌球蛋白重链 IIB 的表达降低，以及 GLUT4 mRNA 水平降低。然而，NF-kB 的遗传阻断不足以恢复 t10，c12-CLA 处理后肌球蛋白重链蛋白表达的降低。令人惊讶的是，与肌管相反，t10，c12-CLA 不能激活成肌细胞中的 NF-kB 转录活性。
总之，t10，c12-CLA 抑制成肌分化和 GLUT4 表达，与 NF-kB 激活无关。
