Timing of Physical Activity on Cardiometabolic Health Outcomes

项目摘要 有规律的体育锻炼能在各种组织中诱导特定的适应性反应，并最终改善健康 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， 许多研究都考察了体力活动的强度、持续时间、频率和方式对 适应性反应。然而，很少考虑体力活动的时间安排。它由来已久。 昼夜节律系统调节心血管功能和新陈代谢，产生~24小时节律 这些生理功能与昼夜周期同步。因此，在不同的体力活动 由于昼夜节律的控制，一天中的不同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，运动对转录产物和代谢产物的影响具有时间依赖性。 代谢途径与运动适应有关，更重要的是，与昼夜节律系统有关。我们 假设体力活动的时间会调节适应性反应，因此可以用来增强 体力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 来自美国国立卫生研究院资助的随机对照试验的数据集，包括生活方式干预和为期一周的加速计 对大约2,200名2型糖尿病患者进行记录，以检查1)时间与 体力活动和心脏代谢健康标记物在基线水平之间的关系，以及2) 1年后的体力活动和心脏代谢健康指标的改善情况。在R00中 阶段，我将通过实验操纵身体活动的时间来测试因果关系 糖尿病前期患者使用随机、交叉设计，实验室内有两个高度对照的 协议。这个创新的项目将促进我们对昼夜节律相互作用影响的了解 系统和体力活动，并可能有助于设计基于证据的生活方式干预措施，包括 体力活动的时间。基于我在时间生物学方面的专业知识，我非常适合进行这项研究， 生理学和人体实验研究；2)卓越的多学科指导团队包括 以及3)支持我职业生涯的无与伦比的研究环境 发展。通过这次学习，我将进一步加强我的昼夜生理学训练，并扩大我的专业知识 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所帮助 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体力活动的相互作用。 这项研究的结果有可能制定出以下基本战略和建议 以时间生物学为基础的运动干预。

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.