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

描述(由申请人提供)：在导致肥胖症流行的众多因素中，食物消费的时机现在被认为是对体重调节的重要贡献。睡眠-觉醒周期从以白天为主的生活方式到夜间生活方式的中断会导致异常的昼夜节律和代谢功能障碍。我们还报告了以进食模式延迟为特征的夜间进食综合征，与体重增加和神经内分泌节律紊乱有关，而没有睡眠-醒来周期的变化。对夜间活动的啮齿动物的研究表明，限制摄食到光期会导致瘦素、胰岛素、皮质酮和甲状腺素的昼夜节律发生深刻变化，并有肥胖、胰岛素抵抗和高脂血症的倾向。然而，使用实验设计，主要是白天进食模式与延迟进食模式对代谢的影响还没有在人类中得到很好的研究。我们假设，延迟的饮食模式，同时保持睡眠唤醒和活动水平不变，将在健康患者中产生体重增加和异常代谢反应。20名体重指数在20-27公斤/平方米的健康男性和女性将被招募参加一项随机交叉实验，测试两种饮食条件。第一种情况是白天进食，在8800小时到1800小时之间吃三顿饭和两份零食。第二种情况是延迟进食，包括在1200小时到22小时之间吃三顿饭和两种零食。这两种饮食条件的能量和常量营养素含量相当，睡眠-觉醒时间在2300小时到0700小时之间保持不变。自愿锻炼将在不同的条件下保持不变。每个参与者都将自由生活，并在第一种情况下从我们的新陈代谢厨房提供两个月的食物，然后是两周的洗涤期，他们通常会像往常一样进食，第二种情况下是两个月(随机分配的顺序)。遵守该协议的情况将受到密切监测，包括食物日志、称重前后的食物、使用通过电子设备发送的图片进行份量评估、活动记录仪以及用于睡眠唤醒和体力活动监测的自我报告。评估电池将发生在四个点：1)基线；2)在第一次两个月进食条件之后；3)在他洗完两周后，开始第二次进食条件；以及4)在第二次两个月进食条件之后。在每个时间点，将使用DEXA测量身体成分，并进行间接量热法。我们将测量血脂、甘油三酯和脂肪酸的空腹水平。分别在0800h、1200h、1600h、2000h和0400h测定血糖、胰岛素、瘦素、脂联素、Ghrelin、皮质醇和褪黑素，比较进食条件对体重、肥胖、能量代谢和激素标志物的影响。这项研究将在自由生活条件下进行，以增加普适性。从这个由R21资助的项目中获得的结果将为更大规模的R01应用奠定可行性。该项目将受益于研究人员在饮食行为、睡眠和昼夜生物学以及神经内分泌学和新陈代谢方面的专业知识，并可能对促进可能影响普通人群体重和代谢健康的健康饮食习惯具有广泛的临床意义。

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.