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IL-15 的表达在大鼠的跑步机跑步反应中增加,并抑制骨骼肌中的内质网应激。

IL-15 expression increased in response to treadmill running and inhibited endoplasmic reticulum stress in skeletal muscle in rats.

机构信息

School of P.E. and Sports Science, Beijing Normal University, Beijing, 100875, China.

出版信息

Endocrine. 2015 Feb;48(1):152-63. doi: 10.1007/s12020-014-0233-y. Epub 2014 Mar 20.

Abstract

Interleukin 15 (IL-15) has recently been proposed as a circulating myokine involved in glucose uptake and utilization in skeletal muscle. However, the role and mechanism of IL-15 in exercise improving insulin resistance (IR) is unclear. Here, we investigated the alteration in expression of IL-15 and IL-15 receptor α (IL-15Rα) in skeletal muscle during treadmill running in rats with IR induced by a high-fat diet (HFD) and elucidated the mechanism of the anti-IR effects of IL-15. At 20 weeks of HFD, rats showed severe IR, with increased levels of fasting blood sugar and plasma insulin, impaired glucose tolerance, and reduced glucose transport activity. IL-15 immunoreactivity and mRNA level in gastrocnemius muscle were decreased markedly as compared with controls. IL-15Rα protein and mRNA levels in both soleus and gastrocnemius muscle were significantly decreased, which might attenuate the signaling or secretion of IL-15 in muscle. Eight-week treadmill running completely ameliorated HFD-induced IR and reversed the downregulated level of IL-15 and IL-15Rα in skeletal muscle of HFD-fed rats. To investigate whether IL-15 exerts its anti-IR effects directly in muscle, we pre-incubated muscle strips with the endoplasmic reticulum stress (ERS) inducer dithiothreitol (DTT) or tunicamycin (Tm); IL-15 treatment markedly decreased the protein expression of the ERS markers 78-kDa glucose-regulated protein, 94-kDa glucose-regulated protein and C/EBP homologous protein and inhibited ERS induced by DTT or Tm. Therefore, treadmill running promoted skeletal IL-15 and IL-15Rα expression in HFD-induced IR in rats. The inhibitory effect of IL-15 on ERS may be involved in improved insulin sensitivity with exercise training.

摘要

白细胞介素 15(IL-15)最近被提出作为一种循环肌因子,参与骨骼肌中的葡萄糖摄取和利用。然而,IL-15 在运动改善胰岛素抵抗(IR)中的作用和机制尚不清楚。在这里,我们研究了高脂饮食(HFD)诱导的 IR 大鼠在跑步机跑步过程中骨骼肌中 IL-15 和 IL-15 受体 α(IL-15Rα)表达的变化,并阐明了 IL-15 抗 IR 作用的机制。在 HFD 的 20 周时,大鼠表现出严重的 IR,空腹血糖和血浆胰岛素水平升高,葡萄糖耐量受损,葡萄糖转运活性降低。与对照组相比,腓肠肌中的 IL-15 免疫反应性和 mRNA 水平明显降低。比目鱼肌和腓肠肌中的 IL-15Rα 蛋白和 mRNA 水平均显著降低,这可能减弱肌肉中 IL-15 的信号转导或分泌。八周的跑步机跑步完全改善了 HFD 诱导的 IR,并逆转了 HFD 喂养大鼠骨骼肌中下调的 IL-15 和 IL-15Rα 水平。为了研究 IL-15 是否直接在肌肉中发挥其抗 IR 作用,我们用内质网应激(ERS)诱导剂二硫苏糖醇(DTT)或衣霉素(Tm)预孵育肌肉条;IL-15 处理显著降低了 ERS 标志物 78-kDa 葡萄糖调节蛋白、94-kDa 葡萄糖调节蛋白和 C/EBP 同源蛋白的蛋白表达,并抑制了 DTT 或 Tm 诱导的 ERS。因此,跑步机跑步促进了 HFD 诱导的 IR 大鼠骨骼肌中 IL-15 和 IL-15Rα 的表达。IL-15 对 ERS 的抑制作用可能与运动训练改善胰岛素敏感性有关。

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