Timing of Physical Activity on Cardiometabolic Health Outcomes

项目摘要 有规律的身体活动会在各种组织中诱导特定的适应性反应，并最终改善健康状况 并降低心血管疾病和2型糖尿病的风险。为了提高体力活动的功效， 许多研究已经检查了身体活动的强度、持续时间、频率和方式对 适应性反应。然而，身体活动的时间很少被考虑。非常确定的 昼夜节律系统调节心血管功能和代谢，产生24小时节律， 在这些与昼夜周期同步的生理功能中。因此，不同时间的体力活动 由于昼夜节律的控制，一天中的时间可能对健康有不同的影响。事实上，最近的突破 动物研究表明，运动对转录物和代谢物的影响依赖于一天中的时间， 代谢途径与运动适应有关，重要的是，与昼夜节律系统有关。我们 假设身体活动的时间调节适应性反应，因此可以用来增强 身体活动带来的健康益处。为了解决这个假设，在K99阶段，我将首先利用 来自NIH资助的随机对照试验的数据集，该试验采用生活方式干预和1周加速计 在大约2,200名2型糖尿病患者中进行记录，以检查1） 体力活动和基线时心脏代谢健康标志物之间的关系，以及2） 体力活动和1年随访时心脏代谢健康标志物的改善。在R 00 阶段，我将通过实验性地操纵身体活动的时间来测试因果关系， 采用随机、交叉设计，在两个高度对照的实验室内， 协议.这个创新的项目将推进我们的知识的相互作用的昼夜节律的时间 系统和身体活动，并可能有助于设计基于证据的生活方式干预措施，将 身体活动的时间。我非常适合进行这项研究，基于1）我在时间生物学方面的专业知识， 生理学和人类实验研究; 2）卓越的多学科指导团队，包括 在各自领域的领导者;和3）无与伦比的研究环境，以支持我的职业生涯 发展通过这项研究，我将进一步我的训练，在昼夜生理学，以及扩大我的专业知识 运动生理学、流行病学和临床试验设计。拟议的研究和培训将有助于 实现我的长期目标，启动一个独立的研究计划，致力于了解 从观察到实验研究设计的昼夜节律系统和身体活动的相互作用。 这项研究的结果有可能为制定基本战略和建议提供框架， 基于时间生物学的运动干预。

Project Summary Regular physical activity induces specific adaptive responses in various tissues, and ultimately improves health and reduces the risk for cardiovascular diseases and type 2 diabetes. To improve the efficacy of physical activity, many studies have examined the impacts of intensity, duration, frequency, and modality of physical activity on the adaptive responses. However, timing of physical activity has been rarely considered. It is well-established that the circadian timing system modulates cardiovascular function and metabolism, generating ~24-h rhythms in these physiological functions that are in synchrony with the day-night cycle. Thus, physical activity at different times of day may have different impacts on health due to the circadian control. Indeed, recent breakthrough animal studies have shown time-of-day dependent effects of exercise on transcripts and metabolites enriched in metabolic pathways that are related to exercise adaptations and, importantly, linked to the circadian system. We hypothesize that timing of physical activity modulates the adaptive responses, and can thus be used to enhance physical activity-induced health benefits. To address this hypothesis, during the K99 phase, I will first utilize the dataset from an NIH-funded randomized controlled trial with lifestyle intervention and 1-week accelerometer recording among approximately 2,200 patients with type 2 diabetes to examine 1) the association between timing of physical activity and markers of cardiometabolic health at baseline, and 2) the association between timing of physical activity and the improvements in markers of cardiometabolic health at 1-year follow-up. In the R00 phase, I will test the causal relationship by experimentally manipulating the timing of physical activity in individuals with prediabetes using a randomized, cross-over design with two highly controlled in-laboratory protocols. This innovative project will advance our knowledge in the interaction effects of the circadian timing system and physical activity and may help in designing evidence-based lifestyle interventions incorporating timing of physical activity. I am well suited to perform this research based on 1) my expertise in chronobiology, physiology, and human experimental research; 2) the exceptional multi-disciplinary mentoring team comprised of leaders in their respective fields; and 3) the unparalleled research environment to support my career development. Through this study, I will further my training in circadian physiology, as well as expand my expertise in exercise physiology, epidemiology, and clinical trial design. The proposed research and training will help achieve my long-term goal of launching an independent research program dedicated to understanding the interaction of the circadian system and physical activity from observational towards experimental study design. The findings of this research have the potential to frame the basic strategy and recommendation of chronobiology-based exercise interventions.