Randomized study of daytime vs. delayed eating: Effect on weight and metabolism

描述（由申请人提供）：在导致肥胖流行的许多因素中，食物消费的时机现在被认为对体重调节有重要贡献。从主要的白天生活方式到夜间生活方式的睡眠-觉醒周期的中断导致昼夜节律异常和代谢功能障碍。我们也报道了夜食综合征，其特征是进食模式延迟，与体重增加和神经内分泌节律紊乱有关，而睡眠-觉醒周期没有改变。对夜间活动的啮齿类动物的研究表明，在光照期限制进食会导致瘦素、胰岛素、皮质酮和甲状腺素的昼夜节律发生深刻变化，并导致肥胖、胰岛素抵抗和高脂血症的倾向。然而，使用实验设计，主要是白天与延迟进食模式的代谢影响尚未在人类中得到很好的研究。我们假设，在保持睡眠-觉醒和活动水平不变的情况下，延迟进食模式会导致健康患者体重增加和代谢反应异常。将招募体重指数在20 - 27 kg/m2之间的20名健康男性和女性进行随机交叉实验，测试两种饮食条件。第一种情况，白天进食，包括三餐和两份零食，在0800到1800之间消耗。第二种情况，延迟进食，包括三餐和两份零食，在1200到2200之间消耗。能量和常量营养素含量在这两种饮食条件下是相当的，睡眠-觉醒时间将在2300到0700之间保持不变。在两种情况下，自愿运动将保持不变。在第一种情况下，每个参与者都是自由生活的，并从我们的代谢厨房里获得食物两个月，然后是两周的清洗期，像往常一样进食，然后是两个月的第二种情况（顺序随机分配）。将通过食物记录、食物称重前后、使用电子设备发送的图片进行份量评估、活动记录仪和自我报告进行睡眠-觉醒和身体活动监测来密切监测方案的遵守情况。评估将在四个点进行：1)基线；2)前2个月进食后的状况；3)洗脱2周后，开始第二次进食前；4)第二个2个月后的进食条件。在每个点，将用DEXA测量身体成分，并进行间接量热。我们将测量空腹血脂、甘油三酯和脂肪酸的水平。葡萄糖、胰岛素、瘦素、脂联素、胃促生长素、皮质醇和褪黑激素将在0800h、1200h、1600h、2000h和0400h测量。我们将比较饮食条件对体重、肥胖、能量代谢和激素指标的影响。这项研究将在自由生活的条件下进行，以增加普遍性。从R21资助的项目中获得的结果将为更大的R01应用建立可行性。该项目将受益于研究人员在饮食行为、睡眠和昼夜节律生物学、神经内分泌学和代谢方面的专业知识，并对促进健康饮食习惯具有潜在的广泛临床意义，这些习惯可能会影响普通人群的体重和代谢健康。

DESCRIPTION (provided by applicant): Of the many factors contributing to the obesity epidemic, timing of food consumption is now recognized for its significant contribution to body weight regulation. Disruption of sleep-wake cycles from a predominantly diurnal lifestyle to a nocturnal lifestyle leads to abnormal circadian rhythms and metabolic dysfunction. We have also reported that night eating syndrome, characterized by a delayed pattern of eating, is associated with weight gain and disruption of neuroendocrine rhythms without sleep-wake cycle changes. Studies in night- active rodents have shown that restriction of feeding to the light period leads t profound changes in the circadian rhythms of leptin, insulin, corticosterone, and thyroxine, and a propensity toward obesity, insulin resistance, and hyperlipidemia. However, the metabolic effects of a predominantly daytime versus delayed eating pattern, using an experimental design, have not been well studied in humans. We hypothesize that a delayed pattern of eating, while keeping sleep-wake and activity levels constant, will produce an increase in weight and an abnormal metabolic response in healthy patients. A total of 20 healthy men and women with a BMI of 20 - 27 kg/m2 will be recruited for a randomized cross-over experiment testing two eating conditions. The first condition, daytime eating, would consist of three meals and two snacks to be consumed between 0800 h and 1800 h. The second condition, delayed eating, would consist of three meals and two snacks consumed between 1200 h and 2200 h. Energy and macronutrient content will be comparable between these eating conditions, and sleep-wake period would be held constant between 2300 h and 0700 h. Voluntary exercise will be held constant between conditions. Each participant would be free-living and supplied food from our metabolic kitchen for two months for the first condition, followed by a two-week wash out period eating as they usually would, followed by two months on the second condition (order randomly assigned). Adherence to the protocol will be monitored closely with food logs, pre- and post- weighing of food, use of pictures sent via electronic devices for portion size assessment, actigraphy, and self- reports for sleep-wake and physical activity monitoring. The assessment battery will occur at four points: 1) baseline; 2) after the first 2-mo eating condition; 3) after he 2-wk washout, before starting the second eating condition; and 4) after the second 2-mo eating condition. At each point body composition will be measured with DEXA and indirect calorimetry will be performed. We will measure fasting levels of lipids, triglycerides, and fatty acids. Glucose, insulin, leptin, adiponectin, ghrelin, cortisol, and melatonin will be measured at 0800h, 1200 h, 1600 h, 2000 h, and 0400 h. We will compare the effects of the eating conditions on weight, adiposity, energy metabolism, and hormonal markers. The study will be performed under free-living conditions to increase generalizability. The results obtained from this R21 funded project will establish feasibility for a larger R01 application. The project will benefit frm the expertise of the investigators in eating behaviors, sleep and circadian biology, and neuroendocrinology and metabolism, and has potentially broad clinical implications for promotion of healthy eating habits that could influence weight and metabolic health in the general population.