Ahn Cheehoon, Hevener Andrea L, Goodyear Laurie J, Bodine Sue C, Esser Karyn A, Seldin Marcus M, Sparks Lauren M
bioRxiv. 2025 May 4:2025.04.29.651323. doi: 10.1101/2025.04.29.651323.
Exercise induces organism-wide molecular adaptations, partly mediated by humoral factors released in response to acute and chronic physical activity. However, the extent and specificity of endocrine effects from training-induced secreted factors remain unclear. Here, we applied systems genetics approaches to quantify inter-organ endocrine networks using multi-tissue transcriptomics and proteomics data collected from endurance-trained rats in The Molecular Transducers of Physical Activity Consortium (MoTrPAC). Eight weeks of endurance training significantly altered both the magnitude and specificity of endocrine effects across multiple origin-target tissue pairs. Subcutaneous white adipose tissue emerged as a key endocrine regulator impacted by training, while extracellular matrix-derived factors were identified as globally regulated secretory features in trained vs sedentary animals. Notably, secretory Wnt signaling factors were identified as key mediators of exercise-induced endocrine adaptations in multiple tissues. Our systems genetics framework provides an unprecedented atlas of inter-organ communication significantly remodeled by endurance exercise, serving as a valuable resource for novel exerkine discovery.
运动可诱导机体产生分子适应性变化，部分是由急性和慢性体育活动所释放的体液因子介导的。然而，训练诱导分泌因子的内分泌效应的程度和特异性仍不清楚。在此，我们应用系统遗传学方法，利用从体力活动分子传感器联盟（MoTrPAC）中耐力训练大鼠收集的多组织转录组学和蛋白质组学数据，对器官间内分泌网络进行量化。八周的耐力训练显著改变了多个源 - 靶组织对之间内分泌效应的大小和特异性。皮下白色脂肪组织成为受训练影响的关键内分泌调节因子，而细胞外基质衍生因子被确定为训练与久坐动物中全局调控的分泌特征。值得注意的是，分泌型Wnt信号因子被确定为运动诱导的多个组织内分泌适应性变化的关键介质。我们的系统遗传学框架提供了一个前所未有的耐力运动显著重塑的器官间通讯图谱，作为发现新型运动因子的宝贵资源。
