Systemic proteomic dynamics of acute exercise reveal genetic links to health and disease

IF 27.5 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism Pub Date : 2026-10-12 DOI:10.1038/s42255-026-01621-w

Nigel Kurgan, Jeppe Kjærgaard, Naja Zenius Jespersen, Virginia Díez-Obrero, Victor Svenstrup, Roger Moreno-Justicia, Sarah Elizabeth Heywood, Cecilie Bergmann Lindqvist, Lisa Ottander, Diana Samodova-Sommer, Alina Malita, Olga Kubrak, Nadja Ahrentløv, Nina Sloth Nielsen, Cody Garett Durrer, Michael Texada, Mathias Ried-Larsen, Simon Rasmussen, Kim Rewitz, Ruth J. F. Loos, Roelof Adriaan Johan Smit, Bente Klarlund Pedersen, Atul Shahaji Deshmukh

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Abstract

Physical activity improves metabolic health, but the molecular responses that mediate its benefits are not fully characterized. Here we present a high-resolution, time-resolved proteomics atlas across plasma, saliva and urine from 25 healthy men in response to acute exercise. We find that exercise regulates more than 3,000 proteins through distinct, fluid-specific temporal dynamics. Network analysis uncovers coordinated remodelling of protein secretion, extracellular matrix and immune activation across body fluids. Replication in an independent cohort shows that many exercise-responsive plasma proteins exhibit consistent responses across age, sex and exercise modalities. Integration with human genome-wide association study data links secreted, exercise-responsive proteins to cardiometabolic diseases. Functional validation of genetically prioritized muscle-specific secreted proteins in Drosophila confirms their role in endurance, behaviour and metabolism. Overall, this open-access atlas ( https://cbmr.ku.dk/research/research-groups/deshmukh-group/shiny-apps/ ) provides a multifluid resource that complements existing exercise-omics efforts for defining molecular adaptations to exercise and for prioritizing candidate exerkines. This study provides a comprehensive, systems-level characterization of acute exercise-induced proteomic responses across several body fluids in humans.

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急性运动的系统蛋白质组动力学揭示了与健康和疾病的遗传联系。

体育活动改善代谢健康，但介导其益处的分子反应尚未完全表征。在这里，我们展示了25名健康男性急性运动后血浆、唾液和尿液的高分辨率、时间分辨蛋白质组学图谱。我们发现运动通过不同的、流体特定的时间动态调节了3000多种蛋白质。网络分析揭示了蛋白质分泌、细胞外基质和免疫激活在体液中的协调重构。在一项独立队列研究中的重复研究表明，许多运动反应血浆蛋白在不同年龄、性别和运动模式下表现出一致的反应。整合人类全基因组关联研究数据，将分泌的运动反应蛋白与心脏代谢疾病联系起来。果蝇基因优先的肌肉特异性分泌蛋白的功能验证证实了它们在耐力，行为和代谢中的作用。总的来说，这个开放获取的图谱（https://cbmr.ku.dk/research/research-groups/deshmukh-group/shiny-apps/）提供了一个多流体资源，补充了现有的运动组学研究成果，用于定义运动的分子适应性和确定候选运动因子的优先级。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

27.50

自引率

2.40%

发文量

170

期刊介绍： Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.