Effects of time-of-day dependent exercise training on social jetlag induced susceptibility to cardiometabolic disease

每日时间依赖性运动训练对社交时差引起的心脏代谢疾病易感性的影响

• 批准号: 10711445
• 负责人: Graham Ripley McGinnis
• 金额: $ 18.88万
• 依托单位: UNIVERSITY OF NEVADA LAS VEGAS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-04 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711445
• 关键词: Acceleration; Acute; Address; Attenuated; Back; Behavior; Behavioral; Body Weight; Cardiometabolic Disease; Cardiovascular Diseases; Cardiovascular Pathology; Cardiovascular system; Cause of Death; Chronic; Circadian Rhythms; Clinical; Cross-Sectional Studies; Darkness; Data; Development; Diabetes Mellitus; Diet; Dietary Intervention; Disease; Disease susceptibility; Exercise; Exposure to; Fatty acid glycerol esters; Female; Fibrosis; Functional disorder; Funding; Gene Expression; Genetic; Genetic Transcription; Glucose; Goals; Health; Heart; Hour; Impairment; Individual; Inflammation; Intervention; Jet Lag Syndrome; Light; Literature; Metabolic; Metabolic Diseases; Metabolic stress; Modeling; Modernization; Molecular; Molecular Analysis; Monitor; Mus; Myocardial; Myocardium; Obesity; Pathology; Pattern; Phase; Physical activity; Physiological; Physiology; Play; Population; Predisposition; Prevention; Research; Role; Running; Schedule; Schools; Signal Transduction; Skeletal Muscle; Societies; Stress; Students; Testing; Time; Tissues; Training; Translating; Treadmill Tests; VO2max; Work; cardiometabolism; cardiorespiratory fitness; cardiovascular disorder prevention; cardiovascular fitness; cardiovascular risk factor; circadian; circadian behavioral rhythms; combat; efficacy evaluation; exercise capacity; exercise intervention; exercise prescription; exercise training; experience; feeding; fitness; improved; innovation; insight; insulin tolerance; male; novel; obesity prevention; preference; preservation; prevent; response; sedentary; sensor; social; training opportunity; western diet

Project Summary This proposal will test the hypothesis that chronic social jetlag attenuates adaptations to exercise training and increases susceptibility to cardiometabolic stress. Social jetlag (SJL) is a novel and pervasive form of circadian rhythm disruption caused by desynchrony between scholastic/professional clocks (i.e. - work or school schedules) and the endogenously driven circadian rhythm (weekend/free day schedules). Recent studies suggest that almost 80% of the population undergoes some degree of SJL (i.e. – ≥1:00 shift between weekday/weekend), with nearly 30% experiencing >2 hours of shifting. Social jetlag has been associated with cardiovascular risk factors and metabolic diseases including obesity, diabetes, and low cardiometabolic fitness (VO2max). However, it is currently unknown how SJL impacts the exercise training response. As exercise is a frontline intervention for the prevention and reversal of cardiovascular and metabolic diseases, it is essential to determine if, and when, exercise can be most effectively prescribed and most protective of the heart. We have previously shown that acute exercise differentially activates myocardial gene expression and signaling depending on the time of day it is performed in mice with intact circadian rhythms. However, it is unclear how exercise, and exercise timing, may be impacted during circadian rhythm disruption via SJL. As such, our overarching hypothesis is that SJL increases the susceptibility to cardiometabolic disease, and the time-of-day that exercise is performed will modulate its efficacy to elicit training adaptations and prevent cardiometabolic disease. To address this hypothesis, we will pursue the following three specific aims. 1) Determine the impact of social jetlag on molecular and physiologic exercise training-induced adaptations in mice, 2) Determine the effects of temporally prescribed exercise during chronic social jetlag on behavioral circadian rhythms, and 3) Determine the impact of chronic social jetlag on cardiometabolic health in mice, and potential reversal with TOD-dependent exercise prescription. Preliminary data presented in this application reveal temporal preference during time- restricted exercise training (i.e. – mice run further during the first half of the active phase compared to the second half), with little difference cardiorespiratory fitness, suggesting exercise training in the late active period may elicit comparable training adaptations with lower volume. How time-restricted voluntary exercise impacts metabolic perturbations during high fat feeding, as well as during SJL, is not currently known. Successful completion of these aims will expand upon these findings to include SJL-induced circadian rhythm disruption, and will increase our understanding on how exercise timing plays a critical role in cardiovascular disease prevention.

项目概要 该提案将检验以下假设：慢性社会时差会减弱对运动训练的适应和 增加对心脏代谢应激的敏感性。社交时差 (SJL) 是一种新颖且普遍的昼夜节律形式 由于学术/专业时钟（即工作或学校）之间的不同步而导致的节奏紊乱 时间表）和内源驱动的昼夜节律（周末/空闲日时间表）。最近的研究 表明几乎 80% 的人口经历了某种程度的 SJL（即 – ≥1:00 之间的转变） 工作日/周末），近 30% 的人经历过超过 2 小时的轮班时间。社交时差与以下因素有关： 心血管危险因素和代谢疾病，包括肥胖、糖尿病和低心脏代谢健康 （最大摄氧量）。然而，目前尚不清楚 SJL 如何影响运动训练反应。由于运动是一种 预防和逆转心血管和代谢疾病的一线干预措施至关重要 确定是否以及何时可以最有效地进行运动并且对心脏最有保护作用。我们有 先前表明，急性运动会差异性地激活心肌基因表达和信号传导 根据一天中的时间，在昼夜节律完整的小鼠中进行。但目前尚不清楚如何 在 SJL 扰乱昼夜节律期间，运动和运动时间可能会受到影响。因此，我们的 总体假设是 SJL 会增加对心脏代谢疾病的易感性，并且一天中的时间 进行的锻炼将调节其功效，以引起训练适应并预防心脏代谢 疾病。为了解决这个假设，我们将追求以下三个具体目标。 1) 确定影响 社会时差对小鼠运动训练引起的分子和生理适应的影响，2) 确定影响 慢性社交时差期间临时规定的运动对行为昼夜节律的影响，以及 3) 确定 慢性社交时差对小鼠心脏代谢健康的影响，以及 TOD 依赖性的潜在逆转 运动处方。本申请中提供的初步数据揭示了时间偏好 限制性运动训练（即，与第二个阶段相比，小鼠在活动阶段的前半段跑得更远） 一半），心肺健康差异不大，表明活动后期的运动训练可能会引起 具有较低训练量的可比训练适应。限时自愿运动如何影响代谢 目前尚不清楚高脂肪喂养期间以及 SJL 期间的扰动。顺利完成 这些目标将在这些发现的基础上进行扩展，包括 SJL 引起的昼夜节律紊乱，并将增加 我们对运动时间如何在心血管疾病预防中发挥关键作用的理解。