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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要该提案将检验以下假设：慢性社会喷气lag削弱了适应运动训练和增加对心脏代谢应激的敏感性。社交喷气式拉格（SJL）是昼夜节律的一种新颖而普遍的形式由学术/专业时钟之间的脱离造成的节奏破坏（即 - 工作或学校时间表）和内源性驱动的昼夜节律（周末/免费日程安排）。最近的研究表明几乎80％的人口经历了一定程度的SJL（即 - ≥1：00 工作日/周末），近30％的经验> 2个小时的转移。社交喷气lag与心血管危险因素和代谢性疾病，包括肥胖，糖尿病和低心脏代谢健康（vo2max）。但是，目前尚不清楚SJL如何影响运动训练的反应。因为运动是预防和逆转心血管和代谢疾病的一线干预，至关重要确定何时以及何时可以最有效地开处方，并且最受到心脏保护。我们有先前表明急性运动会差异激活心肌基因表达和信号传导根据一天中的时间，它在完整的昼夜节律的小鼠中进行。但是，目前尚不清楚如何在昼夜节律中断时，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增加了对心脏代谢疾病的敏感性，并且时间的时间进行该练习将调节其引起训练适应并防止心脏代谢的有效性疾病。为了解决这一假设，我们将追求以下三个具体目标。 1）确定社交喷气式lag在分子和生理运动训练引起的小鼠适应性上，2）确定影响在行为昼夜节律的慢性社会喷气式拉格期间暂时处方的运动，3）确定慢性社会喷气lag对小鼠心脏代谢健康的影响，以及依赖TOD的潜在逆转运动处方。本申请中介绍的初步数据显示在时间期间临时偏好限制运动训练（即 - 小鼠在活动阶段的上半年进一步运行一半），有差异的心脏呼吸适应性，表明活跃时期的运动训练可能会引起可比较的培训适应性较低。时间限制的自愿运动如何影响代谢目前尚不清楚高脂肪进食期间以及SJL期间的扰动。成功完成这些目标将扩大这些发现，包括SJL引起的昼夜节律破坏，并将增加我们对运动时间如何在预防心血管疾病中起关键作用的理解。