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

拟议研究计划耐力运动训练的目标是通过改变中枢(即心脏)和外周(即肌肉内的小血管)机制控制氧气(O2)向需要氧气的肌肉的运输和分配来改善心血管功能。然而，在一些人身上，耐力训练未能实现这一目标。尽管有些人认为遗传因素决定了耐力训练是否会让人受益，但我的实验室的研究表明，如果运动强度适中，每个人都可以改善心血管功能。因此，我提出，通过使用个性化的锻炼计划，准确地考虑到锻炼对身体造成的压力，将使每个人都从耐力训练中受益。我的研究计划的目的是了解在实验条件下控制中枢和外周适应耐力运动训练的机制，在实验条件下，压力水平得到准确的量化。我将探讨有争议的假设：i)当应用适当的运动强度时，运动的所谓“无反应者”并不存在；ii)中枢和外围适应将根据分配给干预的运动强度的不同而做出不同的贡献。科学方法概述I将实施为期10周的耐力训练计划，参与者将被分配到4个训练组：1)中等强度持续运动(MOD；最小身体应激)；2)大强度持续运动1(HVY1；小身体应激)；3)大强度持续运动训练2(HVY2；大身体应激)；4)高强度间歇训练(HIIT；大身体应激)。这一模型的应用将确保锻炼的压力在群体之间不同但在群体内相同。在训练过程中和训练后，使用不同的中枢和外周心血管功能测量，我将确定每组适应的机制。我的实验室拥有独特的设备，可以使用非侵入性或微侵入性方法来执行这项研究计划。新颖性和预期意义目前的方法不足以为参与者规定适当的运动压力。这是一个严重的限制，质疑目前评估耐力训练适应控制机制的方法的有效性。应用一种精确控制运动压力的新运动模型，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)挑战运动的“无反应者”概念。这将为科学家和从业人员提供准确的信息，以便更有效地开展他们的工作，这将做出重大贡献。

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.