Elucidating the critical role of metabolic stress in central and peripheral mechanisms of adaptation to endurance exercise training

耐力运动训练旨在通过改变中枢（即心脏）和外周（即肌肉内的小血管）机制控制氧气（O2）向需要它的肌肉的运输和分配的方式来改善心血管功能。然而，对一些人来说，耐力训练不能达到这个目标。虽然有些人认为遗传因素决定了一个人是否能从耐力训练中受益，但我实验室的研究表明，如果运动训练的强度适当，每个人都能改善心血管功能。因此，我提出，通过使用个性化的运动计划，精确地考虑到运动对身体造成的压力，将使每个人都从耐力训练中受益。我的研究项目的目的是了解在实验条件下控制中枢和外围适应耐力运动训练的机制，在实验条件下，压力水平被精确量化。我将探讨有争议的假设：I)在适当的运动强度下，所谓的运动“无反应”并不存在；ii)中枢和外周适应将根据分配给干预的运动强度做出不同的贡献。我将执行一个为期10周的耐力训练计划，参与者将被分配到4个训练组：1)中等强度的持续运动（MOD；最小的身体压力）；2)大强度连续运动1 （HVY1；小物理应力）；3)大强度连续运动训练2 （HVY2；大生理应激）；4)高强度间歇训练（HIIT；大的身体压力）。该模型的应用将保证运动压力在组间不同，组内相同。通过在训练期间和训练后测量不同的中枢和外周心血管功能，我将确定各组适应的机制。我的实验室有独特的设备来执行这个研究计划，使用非侵入性或微创性的方法。新颖性和预期意义目前的方法不足以规定适当的运动压力给参与者。这是一个关键的限制，质疑当前方法评估控制耐力训练适应机制的有效性。应用一种新的运动模型，精确控制运动的压力，我的研究计划将：1)证明心血管对耐力训练的适应是由干预的压力决定的；2)挑战“无反应”运动的概念。这将为科学家和从业人员提供准确的信息以更有效地开展工作作出重要贡献。

Objectives of proposed research program Endurance exercise training aims to improve cardiovascular function by changing how central (i.e., the heart) and peripheral (i.e., the small vessels within the muscles) mechanisms control the transport and distribution of oxygen (O2) to the muscles that need it. However, in some people, endurance training fails to achieve this goal. Although some believe that genetic factors determine whether someone will benefit from endurance training, work from my laboratory shows that every individual can improve their cardiovascular function if exercise training is of appropriate intensity. Thus, I have proposed that by using a personalized exercise program that precisely considers the stress that the exercise causes to the body will result in everyone benefiting from endurance training. The objective of my research program is to understand the mechanisms that control central and peripheral adaptations to endurance exercise training under experimental conditions where the level of stress is accurately quantified. I will explore the controversial hypotheses that: i) the so-called "non-responders" to exercise do not exist when the appropriate exercise intensity is applied; and ii) central and peripheral adaptations will contribute differently depending on the exercise intensity assigned to the intervention. Summary of scientific approach I will perform a 10-week endurance training program where participants will be assigned to 4 training groups: 1) Moderate intensity continuous exercise (MOD; minimal physical stress); 2) Heavy intensity continuous exercise 1 (HVY1; small physical stress); 3) Heavy intensity continuous exercise training 2 (HVY2; large physical stress); 4) High intensity interval training (HIIT; large physical stress). Application of this model will ensure that the stress of exercise will be different between but identical within groups. Using different measures of central and peripheral cardiovascular function during and after training, I will determine the mechanisms responsible for the adaptations in each group. My laboratory is uniquely equipped to execute this research plan using non-invasive or minimally invasive approaches. Novelty and expected significance Current approaches are inadequate to prescribe the appropriate stress of exercise to participants. This is a critical limitation that questions the validity of current methods to evaluate the mechanisms that control adaptations to endurance training. Applying a novel exercise model that precisely controls the stress of the exercise, my research program will: 1) demonstrate that cardiovascular adaptations to endurance training are determined by the stress of the intervention; 2) challenge the concept of "non-responders" to exercise. This will make a critical contribution providing scientists and practitioners with precise information to perform their work more effectively.