Impact of Daytime vs. Delayed Eating Schedule on Weight and Metabolic Markers Among Obese Persons: An Examination of Circadian Mechanisms

项目概要/摘要 定时进食因其对体重调节的重要贡献而被公认。睡眠-觉醒中断 从主要的昼夜（白天）生活方式到延迟的生活方式的周期导致昼夜节律紊乱 和代谢功能障碍。在我们的R21（DK 100787）中，我们在一个随机的， 交叉设计比较了在白天吃等热量饮食8周与延迟时间表的效果， 有一个恒定的睡眠-觉醒周期。我们的初步结果显示，体重，呼吸商，躯干脂肪，胰岛素， 总胆固醇和脂联素在白天时间表上降低，而甘油三酯和葡萄糖升高 延迟的时间表。此外，在白天的条件下，生长激素释放肽的昼夜节律相提前， 与延迟条件相比，瘦素的延迟，但褪黑激素时相保持不变。我们的研究结果提供 第一个实验证据表明，白天进食与延迟进食相比， 燃料氧化和激素标志物的积极特征，并积极改变正常人的昼夜节律阶段 成年人体重值得注意的是，这种饮食模式的代谢效应及其潜在的昼夜节律机制 还没有在肥胖人群中进行严格的实验研究。我们假设 白天与延迟进食时间表相比，随着睡眠和活动水平的不断提高， 体重，改善代谢概况，并积极影响肥胖者的昼夜调节反应， 降低患代谢综合征和糖尿病的风险。40名健康的男性和女性，年龄21- 50岁，BMI为30-50 kg/m2的受试者将参加一项自由生活的随机交叉实验， 白天进食时间表（0800 h-1900 h）至延迟进食时间表（1200 h-2300 h），能量相当 和常量营养素含量、恒定的睡眠-觉醒时间（2300 h-0700 h）和运动（<30 min/d，<3 d/wk）。 我们的代谢厨房将在每种情况下提供8周的所有食物，中间间隔2周的洗脱期。议定书 遵守将密切监测与食物日志，食物称重，图片的部分大小评估的任何 吃的外部食物，活动记录，以及每日睡眠-觉醒和锻炼的自我报告。将进行评估4 时间，前和后，每个8周的饮食条件，在此期间，我们将测量：体重，身体成分， 呼吸商和静息能量消耗;胰岛素、葡萄糖、胆固醇、甘油三酯的空腹水平， 脂联素、非酯化脂肪酸和C反应蛋白;以及瘦素、饥饿素、褪黑激素、葡萄糖 和皮质醇，以及每4 h（24 h内7次）从外周血中的基因表达，以显示昼夜节律 在饮食条件之间的相位变化。我们还将研究这些变化背后的机制 通过频繁采样的静脉葡萄糖耐量试验，以确定胰岛素敏感性，胰腺β 细胞功能、葡萄糖有效性和游离脂肪酸动力学，并通过皮下白色脂肪 组织基因表达这个多方面的项目将受益于调查人员在饮食方面的专业知识 行为/体重管理、昼夜节律和睡眠生物学、内分泌学和代谢以及生物信息学。

Project Summary/Abstract Timed eating is recognized for its significant contribution to body weight regulation. Disruption of sleep-wake cycles from a predominantly diurnal (daytime) lifestyle to a delayed lifestyle leads to disrupted circadian rhythms and metabolic dysfunction. In our R21 (DK100787), we studied healthy, normal weight adults in a randomized, cross-over design comparing the effects of eating an isocaloric diet for 8 wks on a daytime vs a delayed schedule, with a constant sleep-wake cycle. Our preliminary results indicate weight, respiratory quotient, trunk fat, insulin, total cholesterol, and adiponectin decreased on the daytime schedule, while triglycerides and glucose increased on the delayed schedule. Also, in the daytime condition, the circadian phase of ghrelin was advanced and that of leptin was delayed, but melatonin phase remained unchanged vs. the delayed condition. Our results provide the first experimental evidence that daytime eating compared with delayed eating promotes weight loss and a positive profile for fuel oxidation and hormonal markers, and positively alters circadian rhythm phase in normal weight adults. Notably, the metabolic effects and their underlying circadian mechanisms of such eating patterns have not been investigated rigorously in experimental studies among obese populations. We hypothesize that a daytime compared with a delayed eating schedule, with constant sleep-wake and activity levels, will decrease weight, improve metabolic profiles and positively impact circadian-mediated responses in obese persons, decreasing the risk for developing metabolic syndrome and diabetes. Forty healthy men and women, ages 21- 50, with a BMI of 30-50 kg/m2 will participate in a free-living randomized cross-over experiment comparing a daytime eating schedule (0800h-1900h) to a delayed eating schedule (1200h-2300h), with comparable energy and macronutrient content, and constant sleep-wake periods (2300h-0700h) and exercise (<30 min/d, <3 d/wk). Our metabolic kitchen will provide all food for 8 wks during each condition, separated by a 2-wk washout. Protocol adherence will be monitored closely with food logs, weighing of food, pictures for portion size assessment of any outside food eaten, actigraphy, and daily self-reports of sleep-wake and exercise. Assessments will occur 4 times, pre- and post- each 8-wk eating condition, during which we will measure: weight, body composition, respiratory quotient and resting energy expenditure; fasting levels of insulin, glucose, cholesterol, triglycerides, adiponectin, non-esterified fatty acids and C reactive protein; and levels of leptin, ghrelin, melatonin, glucose and cortisol, and gene expression from peripheral blood every 4h (7 times over 24h) to show circadian rhythm phase changes between the eating conditions. We will also examine mechanisms underlying these changes through frequently sampled intravenous glucose tolerance testing to determine insulin sensitivity, pancreatic beta cell function, glucose effectiveness, and free fatty acid dynamics, and through subcutaneous white adipose tissue gene expression. This multi-faceted project will benefit from the investigators' expertise in eating behaviors/weight management, circadian and sleep biology, endocrinology and metabolism, and bioinformatics.