CONTEXT Exercise training is known to improve glucose tolerance and reverse insulin resistance in persons with obesity. However, some individuals fail to improve or even decline in their clinical traits following exercise intervention. OBJECTIVE This study focused on gene expression and DNA methylation signatures in skeletal muscle of low- (LRE) and high-responders (RES) to 8 weeks of supervised endurance training. METHODS We performed skeletal muscle gene expression and DNA methylation analyses in LRE and RES before and after exercise intervention. Additionally, we applied the least absolute shrinkage and selection operator (LASSO) approach to identify predictive marker genes of exercise outcome. RESULTS We show that the two groups differ markedly already before the intervention. RES were characterized by lower expression of genes involved in DNA replication and repair, and higher expression of extracellular matrix (ECM) components. LASSO approach identified several novel candidates (e.g. ZCWPW2, FOXRED1, STK40), which have not been previously described in the context of obesity and exercise response. Following the intervention, LRE reacted with expression changes of genes related to inflammation and apoptosis, RES with genes related to mitochondrial function. LRE exhibited significantly higher expression of ECM components compared to RES, suggesting improper remodeling and potential negative effects on insulin sensitivity. Between 45 and 70% of differences in gene expression could be linked to differences in DNA methylation. CONCLUSION Together, our data offer an insight into molecular mechanisms underlying differences in response to exercise and provide potential novel markers for the success of intervention.

中文翻译：

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肥胖高反应者和低反应者对耐力运动训练的骨骼肌基因表达特征。

背景 众所周知，运动训练可以改善肥胖症患者的葡萄糖耐量并逆转胰岛素抵抗。然而，一些人在运动干预后未能改善甚至下降其临床特征。目的 本研究重点关注低反应者 (LRE) 和高反应者 (RES) 骨骼肌在 8 周监督耐力训练中的基因表达和 DNA 甲基化特征。方法 我们在运动干预前后对 LRE 和 RES 进行骨骼肌基因表达和 DNA 甲基化分析。此外，我们应用最小绝对收缩和选择算子（LASSO）方法来识别运动结果的预测标记基因。结果我们发现两组在干预前就已经存在显着差异。RES 的特点是参与 DNA 复制和修复的基因表达较低，而细胞外基质 (ECM) 成分表达较高。LASSO 方法确定了几种新的候选药物（例如 ZCWPW2、FOXRED1、STK40），这些候选药物以前在肥胖和运动反应的背景下尚未被描述过。干预后，LRE 与炎症和细胞凋亡相关基因的表达变化发生反应，RES 与线粒体功能相关基因发生反应。与 RES 相比，LRE 的 ECM 成分表达显着较高，表明重构不当并对胰岛素敏感性有潜在的负面影响。45% 到 70% 的基因表达差异可能与 DNA 甲基化的差异有关。结论 总之，我们的数据提供了对运动反应差异背后的分子机制的洞察，并为干预的成功提供了潜在的新标志。