Department of Food and Nutrition, Daegu University, Gyeongsan 38453, South Korea.
Department of Food and Nutrition, Daegu University, Gyeongsan 38453, South Korea.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Jul;1865(7):158678. doi: 10.1016/j.bbalip.2020.158678. Epub 2020 Feb 29.
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‑C]‑oleic acid uptake was not altered while the incorporation of [1‑C]‑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‑C]‑oleic acids and [1‑C]‑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‑C]‑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.
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 Acsl 同工酶之一，尽管其在肌肉能量代谢中的作用尚未得到研究。因此，本研究的目的是使用 siRNA 介导的敲低方法研究 Acsl6 在分化骨骼肌成肌细胞中脂肪酸分配和葡萄糖摄取中的作用。与转染对照 siRNA 的细胞相比，转染 Acsl6 siRNA 的细胞细胞内三酰基甘油（TAG）积累减少。在 Acsl6 敲低的情况下，[1-C]油酸摄取的初始速率没有改变，而[1-C]乙酸掺入总细胞脂质的速率降低（p < 0.05）。在代谢标记研究中，Acsl6 抑制降低了[1-C]油酸和[1-C]乙酸掺入 TAG 和二酰基甘油（DAG）的速率（p < 0.05）。在脉冲-追踪实验的追踪期，Acsl6 抑制增加了细胞内游离脂肪酸并减少了脂肪酸向 TAG 的再酰化通道（p < 0.05）。在 Acsl6 敲低的情况下，标记脂肪酸掺入可溶酸代谢物、β-氧化产物的速率没有改变。Acsl6 siRNA 降低了胰岛素诱导的[1-C]2-脱氧葡萄糖摄取（p < 0.05），但在脂解抑制剂 acipimox 存在下，葡萄糖摄取没有改变。Acsl6 的抑制降低了胰岛素刺激下 Akt 磷酸化和 Glut4 mRNA 表达。这些结果表明，Acsl6 激活并将脂肪酸导向合成途径，并通过重新酯化脂肪酸在骨骼肌中在葡萄糖和脂肪酸循环中发挥作用。
