Impact of sleep and meal timing on food intake regulation.

描述（由申请人提供）：本研究将是第一个测试晚睡和晚吃饭是否会导致正能量平衡和胰岛素抵抗的干预研究。晚睡晚吃的人患肥胖症和代谢紊乱的风险更高。包括我们自己的研究在内的研究表明，睡眠限制会增加食物摄入量，但也有越来越多的证据表明，在白天睡觉，不减少睡眠，可能会导致暴饮暴食，增加胰岛素抵抗（IR）。然而，关于晚睡时间的研究仅限于观察性研究，并因睡眠持续时间的差异而混淆。刺激食欲的神经肽，如神经肽Y （NPY）和下丘脑分泌素-1，也能控制睡眠-觉醒周期，激活大脑奖励区。我们之前已经证明，减少睡眠时间会激活大脑的奖励区域，比如脑岛和眶额皮质。因为饮食是一个强大的外部时间守护者，改变睡眠和吃饭时间的一致性可能会导致激素的变化，这也会影响能量平衡的调节。这项拟议研究的目的是确定晚睡和/或吃东西是否对体重管理和IR有负面影响。这项拟议中的研究将检验这样一种假设，即晚睡晚吃会增加食物摄入量，增强食物的奖励特性，产生表明食欲增强和饱腹感降低的激素谱，以及与早吃早睡相比的IR。这将通过测量随意试餐时和24小时内的食物摄入量、功能性磁共振成像（fMRI；对食物的神经元反应；食物显著性）、食欲调节激素（NPY、下丘脑泌素-1、瘦素、生长素、胰高血糖素样肽1）的测量，以及频繁采样的静脉滴注葡萄糖耐量试验和膳食耐量试验（IR）来评估。38名超重的男性和女性将被招募参加一项为期4期的住院研究。睡眠时间的阶段不同：正常（Ns； 0000-0800小时）或晚睡（Ls； 0330-1130小时）和进餐时间（Nm=醒来后1、5、11和12.5小时进餐；Lm=醒来后4.5、8.5、14.5和16小时进餐）。将测试所有4种组合：Ns/Nm， Ns/Lm， Ls/Nm和Ls/Lm。测量将在睡眠/饮食方案的第三d后进行。血液样本也将分析褪黑激素和皮质醇作为昼夜节律的标志。这项提议的研究将控制睡眠时间和进餐时间，这很重要，因为它将提供关于睡眠和进餐模式影响肥胖和糖尿病风险的机制的信息，而不受睡眠时间的影响。这也将有助于解释肥胖/糖尿病在轮班工作者、受时差/社交时差影响的人以及不吃早餐的人中更普遍的原因。因此，拟议的研究将成为建立和评估影响激素和代谢物节律的生活方式建议或疗法的垫脚石，以防止与白天晚睡和晚吃相关的不良健康影响。

DESCRIPTION (provided by applicant): The proposed study will be the first intervention study to test whether late sleep and meal timing leads to positive energy balance and insulin resistance. Individuals who sleep and eat late into the day are at increased risk of obesity and metabolic disorders. Studies, including our own, have shown that sleep restriction enhances food intake but there is also increasing evidence that sleeping during the daytime hours, without sleep curtailment, may induce overeating and increase insulin resistance (IR). However, studies of late sleep timing are limited to observational studies and confounded by differences in sleep duration. Neuropeptides that stimulate appetite such as neuropeptide Y (NPY) and hypocretin-1 also entrain the sleep-wake cycle and activate brain reward areas. We have previously shown that reducing sleep duration activates brain reward areas, such as the insula and orbitofrontal cortex. Since eating is a strong external time keeper, altering the alignment of sleep and meal times is likely to cause changes in hormones that will also affect energy balance regulation. The goal of the proposed study is to determine whether sleeping and/or eating late in the day has negative consequences for weight management and IR. The proposed study will test the hypothesis that sleeping and eating late in the day will increase food intake, enhance the rewarding properties of food, produce a hormonal profile indicative of enhanced appetite and reduced satiety, as well as IR compared to eating and sleeping at earlier times. This will be assessed by measuring food intake at an ad libitum test meal and over a 24-h period, functional magnetic resonance imaging (fMRI; neuronal responses to food; food salience), measurements of appetite-regulating hormones (NPY, hypocretin-1, leptin, ghrelin, glucagon-like peptide 1), and frequently sampled i.v. glucose tolerance test and meal tolerance test (IR). Thirty-eight overweight men and women will be recruited to participate in a 4-phase inpatient study. Phases will differ in the timing of sleep: normal (Ns; 0000-0800 h) or late (Ls; 0330-1130 h) and alignment of meals (Nm=meals at 1, 5, 11, and 12.5 h after awakening; Lm=meals at 4.5, 8.5, 14.5, and 16 h after awakening). All 4 combinations will be tested: Ns/Nm, Ns/Lm, Ls/Nm, and Ls/Lm. Measurements will be taken after 3 d of the sleep/meal protocol. Blood samples will also be assayed melatonin and cortisol as markers of circadian rhythm. This proposed study, which will manipulate sleep timing and meal timing, is important because it will provide information on the mechanism by which sleep and meal patterns affect obesity and diabetes risk, independent of sleep duration. It will also help explain the greater prevalence of obesity/diabetes 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 and assessment of lifestyle recommendations or therapies that affect hormone and metabolite rhythmicity to prevent the adverse health effects associated with sleeping and eating late during the day.