Alterations in fatty acid metabolism are associated with impaired glucose uptake in skeletal muscle. Long-chain acyl-CoA synthetase (Acsl) 6 is the one of the Acsl isoforms expressed in skeletal muscle although its role in muscle energy metabolism has not been studied. Thus, the aims of this study were to investigate the role of Acsl6 in fatty acid partitioning and glucose uptake in differentiated skeletal myotubes using a siRNA-mediated knockdown approach. Compared with cells transfected with control siRNA, cells transfected with Acsl6 siRNA exhibited reduced intracellular triacylglycerol (TAG) accumulation. The initial rate of [1‑14C]‑oleic acid uptake was not altered while the incorporation of [1‑14C]‑acetic acids into total cellular lipids decreased under Acsl6 knockdown (p < 0.05). In a metabolic labeling study, Acsl6 suppression decreased the incorporation of [1‑14C]‑oleic acids and [1‑14C]‑acetic acids into TAG and diacylglycerol (DAG) (p < 0.05). During the chase period of a pulse-chase experiment, Acsl6 suppression increased the intracellular free fatty acids and decreased the fatty acid channeling toward the reacylation of TAG (p < 0.05). The incorporation of the labeled fatty acids into acid-soluble metabolites, β-oxidation product, was not changed under Acsl6 knockdown. Acsl6 siRNA decreased the insulin-induced uptake of [1‑14C]‑2‑deoxyglucose (p < 0.05) but did not change the glucose uptake in the presence of acipimox, inhibitor of lipolysis. Suppression of Acsl6 deteriorated Akt phosphorylation and Glut4 mRNA expression in response to insulin. These results suggest that Acsl6 activates and channels fatty acids toward anabolic pathways and has a role in glucose and fatty acid cycling through the re-esterification of fatty acids in skeletal muscle.

中文翻译：

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长链酰基辅酶A合成酶的抑制作用可阻断骨骼肌管中的细胞内脂肪酸通量和葡萄糖摄取。

脂肪酸代谢的改变与骨骼肌葡萄糖摄取受损有关。长链酰基辅酶A合成酶（Acsl）6是骨骼肌中表达的一种Acsl亚型，尽管尚未研究其在肌肉能量代谢中的作用。因此，本研究的目的是使用siRNA介导的敲除方法研究Acsl6在分化的骨骼肌管中脂肪酸分配和葡萄糖摄取中的作用。与用对照siRNA转染的细胞相比，用Acsl6 siRNA转染的细胞表现出减少的细胞内三酰基甘油（TAG）积累。在Acsl6敲低的情况下，[1-14C]-油酸的初始摄取速率没有改变，而将[1-14C]-乙酸掺入总细胞脂质中的比例降低了（p <0.05）。在代谢标记研究中，Acsl6抑制作用减少了[1-14C]-油酸和[1-14C]-乙酸在TAG和二酰基甘油（DAG）中的结合（p <0.05）。在脉冲追踪实验的追踪阶段中，Acsl6抑制作用增加了细胞内的游离脂肪酸，并减少了脂肪酸向TAG的重新酰化的通道（p <0.05）。在Acsl6敲低下，标记的脂肪酸向酸溶性代谢物（β-氧化产物）的掺入没有改变。Acsl6 siRNA降低了胰岛素诱导的[1-14C] -2-脱氧葡萄糖的摄取（p <0.05），但在存在脂解抑制剂阿西莫克斯的情况下并未改变葡萄糖的摄取。Acsl6的抑制恶化Akt磷酸化和响应胰岛素的Glut4 mRNA表达。