Reitzner Stefan M, Emanuelsson Eric B, Arif Muhammad, Kaczkowski Bogumil, Kwon Andrew Tj, Mardinoglu Adil, Arner Erik, Chapman Mark A, Sundberg Carl Johan
Department Physiology & Pharmacology, Karolinska Institutet, Solnavägen 9, 171 77 Stockholm, Sweden; Department Women's and Children's Health, Karolinska Institutet, Solnavägen 9, 171 77 Stockholm, Sweden.
Department Physiology & Pharmacology, Karolinska Institutet, Solnavägen 9, 171 77 Stockholm, Sweden.
Mol Metab. 2024 Jan;79:101857. doi: 10.1016/j.molmet.2023.101857. Epub 2023 Dec 21.
Long-term high-level exercise training leads to improvements in physical performance and multi-tissue adaptation following changes in molecular pathways. While skeletal muscle baseline differences between exercise-trained and untrained individuals have been previously investigated, it remains unclear how training history influences human multi-omics responses to acute exercise.
We recruited and extensively characterized 24 individuals categorized as endurance athletes with >15 years of training history, strength athletes or control subjects. Timeseries skeletal muscle biopsies were taken from M. vastus lateralis at three time-points after endurance or resistance exercise was performed and multi-omics molecular analysis performed.
Our analyses revealed distinct activation differences of molecular processes such as fatty- and amino acid metabolism and transcription factors such as HIF1A and the MYF-family. We show that endurance athletes have an increased abundance of carnitine-derivates while strength athletes increase specific phospholipid metabolites compared to control subjects. Additionally, for the first time, we show the metabolite sorbitol to be substantially increased with acute exercise. On transcriptional level, we show that acute resistance exercise stimulates more gene expression than acute endurance exercise. This follows a specific pattern, with endurance athletes uniquely down-regulating pathways related to mitochondria, translation and ribosomes. Finally, both forms of exercise training specialize in diverging transcriptional directions, differentiating themselves from the transcriptome of the untrained control group.
We identify a "transcriptional specialization effect" by transcriptional narrowing and intensification, and molecular specialization effects on metabolomic level Additionally, we performed multi-omics network and cluster analysis, providing a novel resource of skeletal muscle transcriptomic and metabolomic profiling in highly trained and untrained individuals.
长期高水平运动训练可使分子途径发生变化,进而改善身体机能并引发多组织适应性改变。虽然此前已对运动训练者和未训练者之间的骨骼肌基线差异进行过研究,但训练史如何影响人体对急性运动的多组学反应仍不清楚。
我们招募并全面描述了24名个体,他们被分为训练史超过15年的耐力运动员、力量运动员或对照受试者。在进行耐力或阻力运动后的三个时间点,从股外侧肌采集骨骼肌活检样本,并进行多组学分子分析。
我们的分析揭示了分子过程(如脂肪酸和氨基酸代谢)以及转录因子(如HIF1A和MYF家族)的不同激活差异。我们发现,与对照受试者相比,耐力运动员体内肉碱衍生物的丰度增加,而力量运动员体内特定磷脂代谢物增加。此外,我们首次发现急性运动后山梨醇代谢物大幅增加。在转录水平上,我们发现急性阻力运动比急性耐力运动刺激更多的基因表达。这遵循一种特定模式,耐力运动员独特地下调与线粒体、翻译和核糖体相关的途径。最后,两种形式的运动训练都呈现出不同的转录方向特化,与未训练对照组的转录组有所区别。
我们通过转录缩小和强化确定了一种“转录特化效应”,以及代谢组水平上的分子特化效应。此外,我们进行了多组学网络和聚类分析,为训练有素和未训练个体的骨骼肌转录组和代谢组分析提供了新的资源。