NEW YORK – Members of the 'Molecular Transducers of Physical Activity Consortium' (MoTrPAC) have assembled an extensive collection of molecular responses to endurance exercise in rats, uncovering disease-related genes and pathways, tissue-specific effects, and sex-related adaptations over time.

纽约-“体力活动分子传感器联盟”（MoTrPAC）的成员已经收集了大量对大鼠耐力运动的分子反应，揭示了与疾病相关的基因和途径，组织特异性效应以及与性别相关的适应。

'Exercise affects nearly all organ systems in either improving health or reducing disease risk, with beneficial effects resulting from cellular and molecular adaptations within and across many tissues and organ systems,' researchers at Stanford University; the Broad Institute; the University of Iowa; the University of Florida, Gainesville; the University of California, San Diego; and other centers wrote in one of several studies, published in Nature, Nature Communications, and Nature Metabolism on Wednesday..

斯坦福大学（Stanford University）的研究人员说：“运动会影响几乎所有的器官系统，无论是改善健康还是降低疾病风险，都会对许多组织和器官系统内部和之间的细胞和分子适应产生有益的影响。”；布罗德研究所；爱荷华大学；佛罗里达大学盖恩斯维尔分校；加利福尼亚大学圣地亚哥分校；其他中心在周三发表在《自然》、《自然通讯》和《自然新陈代谢》上的几项研究之一中写道。。

For the Nature study, the team performed multiomic analyses on whole blood, blood plasma, and solid samples spanning 18 tissues from male and female 6-month-old laboratory rats that were exposed to up to eight weeks of endurance exercise training.

在《自然》杂志的研究中，该团队对来自6个月大的雄性和雌性实验室大鼠的18个组织的全血、血浆和固体样本进行了多组学分析，这些大鼠接受了长达8周的耐力运动训练。

'We all know exercise is beneficial for us,' co-senior and co-corresponding author Stephen Montgomery, a professor of pathology, genetics, and biomedical data science at Stanford University, said in a statement. 'But we don't know much about the molecular signals that manifest across the body when people exercise, or how they may change when people train.'.

斯坦福大学（StanfordUniversity）病理学、遗传学和生物医学数据科学教授斯蒂芬·蒙哥马利（StephenMontgomery）在一份声明中说，我们都知道锻炼对我们有益但我们不太了解人们运动时在全身表现出来的分子信号，也不知道人们训练时这些信号会发生什么变化。”。

'Our study is the first to take a holistic, bodywide look at molecular changes, from proteins to genes to metabolites to fats and energy production,' Montgomery added. 'It's the broadest profiling yet of the effects of exercise, and it creates an essential map to how it changes the body.'

蒙哥马利补充说：“我们的研究是第一个对分子变化进行整体、全身研究的研究，从蛋白质到基因，从代谢物到脂肪和能量产生。”这是迄今为止对运动效果的最广泛描述，它为运动如何改变身体创建了一个重要的地图。”

For the exercise program, rats were subjected to increasingly challenging treadmill training marked by gradual upticks in incline, speed, and duration over one, two, four, or eight weeks, they explained, with tissue samples collected 48 hours after the last round of exercise.

他们解释说，在运动计划中，大鼠接受越来越具有挑战性的跑步机训练，其特征是在一周，两周，四周或八周内逐渐增加坡度，速度和持续时间，并在最后一轮运动后48小时收集组织样本。

Based on genomic, transcriptomic, proteomic, metabolomic, epigenomic, lipidomic, immune system, phosoproteome, acetylproteome, and ubiquitylproteome profiles generated with more than two dozen molecular platforms and nearly 9,500 assay types, the team untangled molecular responses turning up within and across different tissue types over time along the rats' training journey..

基于基因组学、转录组学、蛋白质组学、代谢组学、表观基因组学、脂质组学、免疫系统、磷酸化蛋白质组、乙酰化蛋白质组和泛素化蛋白质组谱，该团队通过二十多个分子平台和近9500种分析类型生成，解开了大鼠训练过程中随着时间的推移在不同组织类型内部和之间出现的分子反应。。

'[W]e identified thousands of training-induced changes within and across tissues, including temporal and sex-biased responses, in mRNA transcripts, proteins, post-translational modifications, and metabolites,' the authors reported. 'Each omic dataset provides unique insights into exercise adaptation, where a holistic understanding requires multiomic analysis.'.

作者报道说：“我们在mRNA转录本、蛋白质、翻译后修饰和代谢物中发现了数千种训练引起的组织内和组织间的变化，包括时间和性别偏向反应。”每个组学数据集都提供了对运动适应的独特见解，其中整体理解需要多组学分析。”。

Along with such molecular and tissue-related shifts in the endurance exercise-exposed rats compared with their sedentary counterparts, the investigators documented distinct physical changes in the animals.

与久坐的大鼠相比，耐力运动暴露的大鼠发生了这种分子和组织相关的变化，研究人员记录了动物明显的身体变化。

While male rats had lower body fat after exercise, for example, body weight increased in female rats, and aerobic capacity increased in rats from both sexes. In addition, exercise did not lead to body fat declines in the female animals, though sedentary control animals did show an uptick in body fat in the female rats..

例如，运动后雄性大鼠的体脂含量较低，而雌性大鼠的体重增加，两性大鼠的有氧能力增加。此外，运动并没有导致雌性动物的体脂下降，尽管久坐的对照动物确实显示雌性大鼠的体脂增加。。

In particular, the team saw endurance training adaptations that affected pathways involved in everything from stress or immune responses to metabolic processes or mitochondrial organelle function, among many other molecular and network changes.

特别是，该团队看到耐力训练的适应性影响了从压力或免疫反应到代谢过程或线粒体细胞器功能以及许多其他分子和网络变化的所有途径。

While gene activity and regulation varied across tissues tested to some extent, a set of 22 genes involved in pathways for heat shock proteins, tissue remodeling, blood pressure, insulin sensitivity, the immune system, and other pathways showed exercise-related shifts in the heart, lung, liver, kidney, a calf muscle called the gastrocnemius, and subcutaneous white adipose tissue..

虽然测试的组织中的基因活性和调控在一定程度上有所不同，但涉及热休克蛋白，组织重塑，血压，胰岛素敏感性，免疫系统和其他途径的一组22个基因显示出与运动相关的心脏，肺，肝，肾，称为腓肠肌的小腿肌肉和皮下白色脂肪组织的变化。。

'[W]e present the first whole-organisms molecular map of the temporal effects of endurance exercise training in male and female rats and provide multiple insights enabled by this MoTrPAC multiomic data resource,' the authors reported, noting that 'data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository.'.

“我们展示了第一个关于耐力运动训练对雄性和雌性大鼠的时间影响的全生物分子图谱，并提供了这种MoTrPAC多组学数据资源所提供的多种见解，”作者报告说，并指出“本研究中提供的数据和分析将作为理解和探索耐力训练的多组织分子效应的宝贵资源，并在公共存储库中提供。”。

Although the study was done in rats, the investigators explained, they saw overlap with exercise-related processes previously found in humans, as well as links to conditions such as tissue injury and repair, cardiovascular health, non-alcoholic fatty liver disease, and inflammatory bowel disease.

研究人员解释说，虽然这项研究是在大鼠身上进行的，但他们发现与先前在人类身上发现的运动相关过程有重叠，以及与组织损伤和修复、心血管健康、非酒精性脂肪肝和炎症性肠病等疾病的联系。

'This MoTrPAC resource provides future opportunities to enhance and refine the molecular map of the endurance training response,' the authors wrote. 'We expect that this dataset will remain an ongoing platform to translate tissue- and sex-specific molecular changes in rats to humans.'

作者写道：“这种MoTrPAC资源为增强和完善耐力训练反应的分子图谱提供了未来的机会。”我们预计，这个数据集将继续成为一个平台，将大鼠组织和性别特异性分子变化转化为人类。”

In a related Nature Communications paper, Stanford University researchers Stephen Montgomery, Nikolai Vetr, and colleagues studied the gene regulatory consequences of the rats' exercise regimes, particularly when it came to regulatory features with ties to 114 complex traits and conditions.

斯坦福大学研究人员斯蒂芬·蒙哥马利（StephenMontgomery）、尼古拉·维特（NikolaiVetr）及其同事在《自然通讯》（Nature Communications）的一篇相关论文中研究了大鼠运动方式的基因调控后果，特别是当涉及到与114种复杂性状和条件相关的调控特征时。

The team was able to tease out more than 5,500 trait-tissue-gene relationships that are expected to be relevant in humans by analyzing results from MoTrPAC alongside tissue-specific expression quantitative trait data from the Genotype-Tissue Expression (GTEx) project, data from 114 genome-wide association studies encompassing a dozen traits or disease types, data from transcriptome-wide association studies, and more..

该团队通过分析来自MoTrPAC的结果以及来自基因型组织表达（GTEx）项目的组织特异性表达数量性状数据，来自114个全基因组关联研究的数据，包括十几种性状或疾病类型，来自转录组范围关联研究的数据等，能够梳理出预计与人类相关的5500多种性状-组织-基因关系。。

'In our study, we have identified multiple tissues and tissue-by-gene pairs where exercise may modify disease risk through gene expression,' the author reported, noting that '[d]espite human-rat differences, our unbiased approach identified multiple results that echo established exercise-disease relationships.'.

“在我们的研究中，我们已经确定了多个组织和逐个基因对的组织，其中运动可能通过基因表达改变疾病风险，”作者报告说，并指出，“尽管人类与大鼠之间存在差异，但我们的无偏方法确定了多个结果，这些结果反映了已建立的运动-疾病关系。”。

In another study, published in Nature Metabolism, investigators from UCSD, Duke University Medical Center, the Oklahoma Medical Research Foundation, the University of Iowa, Pacific Northwest National Laboratory, and elsewhere used MoTrPAC data to explore biological sex-specific responses to exercise training in subcutaneous white adipose tissue from rats exposed to such training..

在另一项发表在《自然代谢》上的研究中，来自UCSD、杜克大学医学中心、俄克拉荷马医学研究基金会、爱荷华大学、太平洋西北国家实验室和其他地方的研究人员使用MoTrPAC数据来探索暴露于这种训练的大鼠皮下白色脂肪组织中运动训练的生物性别特异性反应。。

The study 'underscores the powerful impact of sex on adipose tissue biology,' the authors wrote, 'and provides a rich resource to investigate the [subcutaneous white adipose tissue] response to [exercise training].'

作者写道，这项研究“强调了性别对脂肪组织生物学的强大影响，并为研究[皮下白色脂肪组织]对[运动训练]的反应提供了丰富的资源。”