Department of Biology, York University, Toronto, Ontario, Canada M3J 1P3.
J Mol Endocrinol. 2013 Jun 29;51(1):155-65. doi: 10.1530/JME-13-0059. Print 2013.
Previous studies have shown that many metabolic actions of adiponectin are mediated via the activation of AMP kinase and that adiponectin stimulates GLUT4 translocation and glucose uptake in the muscle. In this study, we demonstrate that adiponectin stimulates actin cytoskeleton remodeling, with increased phosphorylation of cofilin, and that blocking of cytoskeletal remodeling with cytochalasin D prevents adiponectin-stimulated AMPK phosphorylation in L6 myoblasts. LKB1 is an upstream kinase of AMPK, and we observed the colocalization of LKB1 with filamentous actin in response to adiponectin. Adiponectin-stimulated translocation of LKB1 from a nuclear to a cytoplasmic location to activate AMPK was also dependent on actin cytoskeleton remodeling. Cytoskeletal remodeling visualized by rhodamine-phalloidin immunofluorescence indicated that adiponectin-stimulated reorganization resulted in the formation membrane ruffles, which were also clearly visible by scanning electron microscopy in L6-GLUT4(myc) myoblasts. The stimulation of glucose uptake, but not of GLUT4-myc translocation to the cell surface, by adiponectin was also dependent on actin cytoskeleton remodeling. These results suggest that actin remodeling induced by adiponectin is essential for mediating LKB1/AMPK signaling and glucose uptake in skeletal muscle cells.
先前的研究表明，脂联素的许多代谢作用是通过激活 AMP 激酶介导的，脂联素刺激肌肉中的 GLUT4 易位和葡萄糖摄取。在这项研究中，我们证明脂联素刺激肌动蛋白细胞骨架重塑，伴丝切蛋白磷酸化增加，用细胞松弛素 D 阻断细胞骨架重塑可防止脂联素刺激 L6 成肌细胞中 AMPK 的磷酸化。LKB1 是 AMPK 的上游激酶，我们观察到 LKB1 与丝状肌动蛋白的共定位响应脂联素。脂联素刺激 LKB1 从核到细胞质位置的易位以激活 AMPK 也依赖于细胞骨架重塑。通过 rhodamine-phalloidin 免疫荧光显示细胞骨架重塑表明，脂联素刺激的重排导致形成膜皱襞，在 L6-GLUT4(myc)成肌细胞中也可以通过扫描电子显微镜清楚地看到。脂联素刺激的葡萄糖摄取增加，但不是 GLUT4-myc 易位到细胞表面，也依赖于肌动蛋白细胞骨架重塑。这些结果表明，脂联素诱导的肌动蛋白重塑对于介导骨骼肌细胞中的 LKB1/AMPK 信号传导和葡萄糖摄取是必需的。
