Phosphoproteomics uncovers exercise intensity-specific signaling networks underlying high-intensity interval training in human skeletal muscle

Nolan J Hoffman, Jamie Whitfield, Di Xiao, Bridget E Radford, Veronika Suni, Ronnie Blazev, Pengyi Yang, Benjamin L Parker, John A Hawley
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Abstract

In response to exercise, protein kinases and signaling networks are rapidly engaged in skeletal muscle to maintain energy homeostasis. High-intensity interval training (HIIT) induces superior or similar health-promoting skeletal muscle and whole-body adaptations compared to prolonged, moderate-intensity continuous training (MICT). However, the exercise intensity-specific signaling pathways underlying HIIT versus MICT are unknown. Ten healthy male participants completed bouts of work- and duration-matched HIIT and MICT cycling in randomized crossover trials. Mass spectrometry-based phosphoproteomic analysis of human muscle biopsies mapped acute signaling responses to HIIT and MICT, identifying 14,931 phosphopeptides and 8,509 phosphosites. Bioinformatics uncovered >1,000 phosphosites significantly regulated by HIIT and/or MICT, including 92 and 348 respective HIIT-specific phosphosites after 5 and 10 min and >3,000 total phosphosites significantly correlated with plasma lactate. This first human muscle HIIT signaling network map has revealed rapid exercise intensity-specific regulation of kinases, substrates and pathways that may contribute to HIIT's unique health-promoting effects.
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磷蛋白组学揭示了人体骨骼肌高强度间歇训练的运动强度特异性信号网络
运动时,骨骼肌中的蛋白激酶和信号网络会迅速参与以维持能量平衡。与长时间、中等强度的持续训练(MICT)相比,高强度间歇训练(HIIT)能诱导更好或类似的促进健康的骨骼肌和全身适应性。然而,HIIT 与 MICT 的运动强度信号传导途径尚不清楚。在随机交叉试验中,10 名健康男性参与者分别完成了与工作强度和持续时间相匹配的 HIIT 和 MICT 自行车运动。对人体肌肉活检组织进行的基于质谱的磷酸化蛋白质组分析绘制了HIIT和MICT的急性信号反应图,确定了14,931个磷酸肽和8,509个磷酸位点。生物信息学发现了 1000 个受 HIIT 和/或 MICT 显著调控的磷酸位点,包括 92 个和 348 个分别在 5 分钟和 10 分钟后受 HIIT 特异性调控的磷酸位点,以及 3000 个与血浆乳酸显著相关的磷酸位点。这是首个人类肌肉 HIIT 信号网络图,它揭示了激酶、底物和通路的快速运动强度特异性调控,这些可能有助于 HIIT 的独特健康促进作用。
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