Impact of circadian misalignment on energy balance regulation

这项拟议中的研究将测试进食时间与睡眠时间的不一致是否会导致 积极的能量平衡和身体成分的变化。睡得晚、吃得晚的人 患肥胖症和代谢紊乱的风险增加。这可能是由于神经肽的活性， 激活大脑奖励区域并刺激食物摄入，这也参与了睡眠-觉醒周期。我们 已经表明，睡眠限制会激活大脑的奖励区域，如大脑皮层和眶额皮层， 增加食物摄入量，但也有越来越多的证据表明，在一天中错误的时间进食（即在 动物的休息期或人类的一天中的晚些时候），可能促进体重增加/阻碍体重减轻。 然而，晚餐时间的研究仅限于观察性研究，并受到以下差异的混淆： 睡眠时间和时间。由于进食是一个强大的外部时间守护者，我们假设，改变饮食习惯， 睡眠和进餐时间的一致会导致调节能量平衡的荷尔蒙的变化。的目标 这项拟议中的研究是为了确定与睡眠不同步的饮食是否会对 体重管理拟议的研究既有机械和翻译的目标。首先，我们将测试 在一天中晚些时候进食将促进积极的能量平衡（机械目标1和2）的假设， 增强食物的奖励特性，改变食欲调节激素和能量消耗 与以前的饮食相比。这将通过测量神经元对食物的反应（功能性）来评估。 磁共振成像）、食欲调节激素（瘦素、胃饥饿素、胰高血糖素样肽1、肽 YY）和24小时能量消耗（代谢室）。接下来，我们将测试 假设4周的自由生活条件的不一致的膳食，相对于调整膳食，将导致 增加能量摄入和身体脂肪（转化目标3）。44名超重的男女将被 招募参与一项2阶段交叉研究，睡眠时间恒定。相位只会在 膳食与睡眠期的一致性：一致=醒来后1小时开始进餐;不一致=进餐 从觉醒后5小时开始。将从3天和14天后的测量中解决机制目标。 干预。将分析血样中褪黑激素和皮质醇作为昼夜节律的标志物。的 翻译目标将在规定的进餐时间后的4周自由生活期后解决， 相位这项拟议中的研究将在不影响总睡眠时间的情况下控制进餐时间， 因为它将提供关于昼夜节律失调影响肥胖风险的机制的信息， 与睡眠时间无关。它还将提供信息，以帮助解释肥胖症的更大流行率 轮班工作者、受时差/社交时差影响的人和不吃早餐的人。因此，拟议的研究将 成为建立生活方式建议或疗法的垫脚石，以个性化时钟类型 以改善体重管理和降低心脏代谢风险。

The proposed study will test whether the misalignment of eating occasions to the sleep period leads to positive energy balance and body composition changes. Individuals who sleep and eat late into the day are at increased risk of obesity and metabolic disorders. This may be due to the activity of neuropeptides that activate brain reward areas and stimulate food intake, which are also involved in the sleep-wake cycle. We have shown that sleep restriction activates brain reward areas, such as the insula and orbitofrontal cortex, and enhances food intake but there is also increasing evidence that eating at the wrong time of day (i.e. during resting periods in animals or later in the day in humans), may promote weight gain/hinder weight loss. However, studies of late meal timing are limited to observational studies and confounded by differences in sleep duration and timing. Since eating is a strong external time keeper, we hypothesize that altering the alignment of sleep and meal times will cause changes in hormones that regulate energy balance. The goal of the proposed study is to determine whether eating out of synchrony with sleep has negative consequences for weight management. The proposed study has both mechanistic and translational objectives. First, we will test the hypothesis that eating late in the day will promote positive energy balance (mechanistic aims 1 & 2) by enhancing the rewarding properties of food, altering appetite-regulating hormones, and energy expenditure compared to eating at earlier times. This will be assessed by measuring neuronal responses to food (functional magnetic resonance imaging), appetite-regulating hormones (leptin, ghrelin, glucagon-like peptide 1, peptide YY), and 24-h energy expenditure (metabolic chamber) under controlled feeding conditions. Next, we will test the hypothesis that 4 wk of free-living conditions of misaligned meals, relative to aligned meals, will lead to increases in energy intake and body fat (translational aim 3). Forty-four overweight men and women will be recruited to participate in a 2-phase, crossover study, with constant sleep periods. Phases will only differ in the alignment of meals to the sleep period: aligned = meals starting 1 h after awakening; misaligned = meals starting 5 h after awakening. Mechanistic aims will be addressed from measurements taken after 3 and 14 d of the intervention. Blood samples will be assayed for melatonin and cortisol as markers of circadian rhythm. The translational aim will be addressed after a 4 wk free-living period following the prescribed meal times for each phase. This proposed study, which will manipulate meal timing, without affecting total sleep time, is important because it will provide information on the mechanism by which circadian misalignment influences obesity risk, independent of sleep duration. It will also provide information to help explain the greater prevalence of obesity in shift workers, those affected by jetlag/social jetlag, and breakfast skippers. As such, the proposed study will be a stepping-stone in the establishment of lifestyle recommendations or therapies to personalize chronotype to improve weight management and cardio-metabolic risk reduction.