Skeletal muscle, a highly metabolic tissue, is particularly vulnerable to increased levels of saturated free fatty acids (FFAs). The role of autophagy in saturated FFAs-induced cellular senescence and insulin resistance in skeletal muscle remains unclear. Therefore, the present study was aimed to explore autophagic flux in cellular senescence and insulin resistance induced by palmitate in muscle cells, and whether resveratrol limited these responses. Our results showed that palmitate induced cellular senescence in both myoblasts and myotubes. In addition, palmitate delayed differentiation in myoblasts and inhibited expression of insulin-stimulated p-AKTSer473 in myotubes. The accumulations of autophagosome assessed by tandem fluorescent-tagged LC3 demonstrated that autophagic flux was impaired in both palmitate-treated myoblasts and myotubes. Resveratrol protected muscle cells from palmitate-induced cellular senescence, apoptosis during differentiation, and insulin resistance via ameliorating autophagic flux. The direct influence of autophagic flux on development of cellular senescence and insulin resistance was confirmed by blockage of autophagic flux with chloroquine. In conclusion, impairment of autophagic flux is crucial for palmitate-induced cellular senescence and insulin resistance in muscle cells. Restoring autophagic flux by resveratrol could be a promising approach to prevent cellular senescence and ameliorate insulin resistance in muscle.

中文翻译：

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白藜芦醇通过改善自噬通量保护肌肉细胞免受棕榈酸酯诱导的细胞衰老和胰岛素抵抗

骨骼肌是一种高度代谢的组织，特别容易受到饱和游离脂肪酸 (FFA) 水平升高的影响。自噬在饱和 FFA 诱导的骨骼肌细胞衰老和胰岛素抵抗中的作用仍不清楚。因此，本研究旨在探讨棕榈酸酯在肌肉细胞中诱导的细胞衰老和胰岛素抵抗中的自噬通量，以及白藜芦醇是否限制了这些反应。我们的研究结果表明，棕榈酸盐可诱导成肌细胞和肌管中的细胞衰老。此外，棕榈酸酯延迟了成肌细胞的分化并抑制了肌管中胰岛素刺激的 p-AKTSer473 的表达。通过串联荧光标记的 LC3 评估的自噬体积累表明，棕榈酸盐处理的成肌细胞和肌管中的自噬通量均受损。白藜芦醇通过改善自噬通量保护肌肉细胞免受棕榈酸酯诱导的细胞衰老、分化过程中的细胞凋亡和胰岛素抵抗。自噬通量对细胞衰老和胰岛素抵抗发展的直接影响通过用氯喹阻断自噬通量得到证实。总之，自噬通量的损害对于棕榈酸酯诱导的肌肉细胞衰老和胰岛素抵抗至关重要。通过白藜芦醇恢复自噬通量可能是预防细胞衰老和改善肌肉胰岛素抵抗的有前景的方法。自噬通量对细胞衰老和胰岛素抵抗发展的直接影响通过用氯喹阻断自噬通量得到证实。总之，自噬通量的损害对于棕榈酸酯诱导的肌肉细胞衰老和胰岛素抵抗至关重要。通过白藜芦醇恢复自噬通量可能是预防细胞衰老和改善肌肉胰岛素抵抗的有前景的方法。自噬通量对细胞衰老和胰岛素抵抗发展的直接影响通过用氯喹阻断自噬通量得到证实。总之，自噬通量的损害对于棕榈酸酯诱导的肌肉细胞衰老和胰岛素抵抗至关重要。通过白藜芦醇恢复自噬通量可能是预防细胞衰老和改善肌肉胰岛素抵抗的有前景的方法。