Mechanisms addressing the causal relationships of sleep, circadian rhythms, and cardiometabolic health

现代生活方式导致了睡眠不足和行为与内源性生物钟的错位， 它是由明暗循环控制的。由此产生的对睡眠质量和昼夜节律的有害影响 与困扰着很大一部分人口的过多慢性病有关。具体来说， 睡眠时间短、睡眠质量差/睡眠障碍和昼夜节律失调与 肥胖和心血管疾病的风险增加。然而，这些联系的因果关系及其 潜在的机制尚未完全揭开。在试图揭示不足的因果影响时 睡眠对肥胖的影响，我们的实验室表明，严重的睡眠限制上调了与之有关的神经元奖赏网络 在享乐主义的食物消费中，导致能量的摄入，特别是来自脂肪的能量，相对于充足的 睡吧。其他人也表明，这些睡眠操作会导致深夜进食，这可能会导致 昼夜节律失调。然而，急性睡眠限制(每晚4小时，连续5晚)并不是一种典型的行为 我们现在正在测试更长时间、更温和形式的睡眠限制以及延长生理周期的影响 不协调，对能量平衡和心血管疾病风险。这项拟议研究的主要目的是 计划是阐明睡眠模式和生活方式行为的一致性的途径，即食物 消费、活动和睡眠相互影响着肥胖和心血管疾病的风险。我们建议 操纵睡眠和昼夜节律的男性和女性的机械性临床干预研究 暴露于心脏代谢危险因素。这些随机对照干预措施将包括以下结果 如能量平衡(食物摄入量、能量消耗和身体成分的测量)和 心血管疾病危险因素(细胞和全身炎症、免疫功能、血糖调节、 血压)。男性和女性将被纳入同等数量的研究，以评估这些途径是否与 睡眠不佳和昼夜节律失调对心脏代谢风险的影响因性别而异。我们计划利用研究的灵活性 由这一赠款机制提供，以扩大与相关和互补领域的调查人员的合作 研究，导致实验室之间分享技术和研究范例，培训研究员和 未来在睡眠、昼夜节律和心脏代谢健康领域的研究人员，并提高认识 睡眠和生活方式行为与生物钟的一致性对于最佳健康的重要性。

Modern lifestyles have led to short sleep and misalignment of behaviors to the endogenous circadian clock, which is governed by the light-dark cycle. The resulting deleterious effects on sleep quality and circadian rhythms have been associated with a plethora of chronic diseases that afflict a large portion of the population. Specifically, short sleep duration, poor quality sleep/sleep disorders, and circadian misalignment have been associated with an increased risk of obesity and cardiovascular disease. However, the causality of these associations and their underlying mechanisms have yet to be fully uncovered. In attempting to uncover the causal impact of insufficient sleep on obesity, our lab has shown that acute sleep restriction upregulates neuronal reward networks implicated in hedonic food consumption and results in higher intake of energy, particularly from fat, relative to adequate sleep. Others have also shown that these sleep manipulations drive late-night eating, which may then cause circadian misalignment. However, acute sleep restriction (<4 h of sleep/night for 5 nights) is not a typical behavior and we are now testing the impact of longer, milder forms of sleep restriction as well as prolonged circadian misalignment, on energy balance and cardiovascular disease risk. The main objective of this proposed research program is to elucidate the pathways by which sleep patterns and alignment of lifestyle behaviors, namely food consumption, activity, and sleep, to one another influence obesity and cardiovascular disease risk. We propose mechanistic clinical intervention studies in men and women that manipulate sleep and circadian rhythms as exposures on cardiometabolic risk factors. These randomized controlled interventions will include outcomes such as energy balance (measurements of food intake, energy expenditure, and body composition) and cardiovascular disease risk factors (cellular and systemic inflammation, immune function, glucose regulation, blood pressure). Men and women will be enrolled in equal numbers to assess whether the pathways that related poor sleep and circadian misalignment to cardiometabolic risk differ by sex. We plan to use the research flexibility afforded by this grant mechanism to expand collaborations with investigators in related and complementary fields of research, resulting in sharing of techniques and research paradigms between laboratories, train fellows and future investigators in the fields of sleep, circadian rhythms, and cardiometabolic health, and promote awareness of the importance of sleep and alignment of lifestyle behaviors to circadian clocks for optimal health.