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

项目摘要/摘要 限时进食因其对体重调节的重大贡献而被公认。睡眠-觉醒中断 从白天为主的生活方式转变为延迟的生活方式会导致昼夜节律被打乱 和代谢功能障碍。在我们的R21(DK100787)中，我们以随机、 交叉设计比较了白天吃8周等卡路里饮食和推迟进食时间表的效果， 有一个持续的睡眠-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减少，而甘油三酯和葡萄糖增加 在被推迟的日程上。此外，在白天条件下，Ghrelin的昼夜节律期提前， 与延迟状态相比，瘦素水平延迟，但褪黑素时相保持不变。我们的结果提供了 第一个实验证据表明，与延迟进食相比，白天进食可以促进减肥和 燃料氧化和激素标志物阳性，并正向改变正常的昼夜节律相 体重过重的成年人。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 在肥胖人群中的实验研究中没有得到严格的调查。我们假设一个 与延迟的进食时间表相比，白天的睡眠和活动水平将会减少 体重，改善代谢状况，积极影响肥胖者的昼夜节律反应， 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，21岁- 50，体重指数在30-50公斤/平方米的人将参加一项自由生活的随机交叉实验，比较 白天进食时间表(0800h-1900h)改为延迟进食时间表(1200h-2300h)，能量相当 和大量营养素含量，以及持续的睡眠-觉醒时间(2300h-0700h)和运动(30min/d，3d/wk)。 我们的新陈代谢厨房将在每种情况下提供8周的所有食物，由2周的洗涤隔开。协议 遵守情况将通过食物记录、食物重量、用于评估食物份量的图片进行密切监测 户外饮食，活动记录，每天的睡眠自我报告--醒来和锻炼。将进行评估4 每次8周的进食情况，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；空腹胰岛素、葡萄糖、胆固醇、甘油三酯、 脂联素、非酯化脂肪酸和C反应蛋白；瘦素、胃促生长素、褪黑素和血糖水平 和皮质醇，以及每隔4小时(24小时内7次)外周血中的基因表达，以显示昼夜节律 进食条件之间的相变。我们还将研究这些变化背后的机制 通过频繁采集静脉葡萄糖耐量试验来确定胰岛素敏感性，胰岛β 细胞功能、葡萄糖有效性和游离脂肪酸动态，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、内分泌学和新陈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.