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

白天与延迟饮食计划对肥胖者体重和代谢标志物的影响：昼夜节律机制的检查

• 批准号: 9453152
• 负责人: KELLY C ALLISON
• 金额: $ 75万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9453152
• 关键词: Adherence; Adipose tissue; Adult; Age; Bioinformatics; Biology; Blood; Blood Chemical Analysis; Body Composition; Body Weight; Body Weight decreased; C-reactive protein; Cell physiology; Cholesterol; Circadian Rhythms; Clinical; Crossover Design; Diabetes Mellitus; Diet; Diet Habits; Eating; Eating Behavior; Effectiveness; Endocrinology; Energy Intake; Energy Metabolism; Exercise; Fasting; Fatty acid glycerol esters; Food; Functional disorder; Gene Expression; Genes; Glucose; Guidelines; Health; Homeostasis; Hormonal; Hormones; Hydrocortisone; Insulin; Intervention; Leg; Leptin; Life Style; Macronutrients Nutrition; Measures; Mediating; Medical; Melatonin; Metabolic; Metabolic Diseases; Metabolic Marker; Metabolic syndrome; Molecular Profiling; Monitor; Nonesterified Fatty Acids; Obesity; Patient Self-Report; Pattern; Persons; Phase; Phenotype; Population; Protocols documentation; Randomized; Recommendation; Regulation; Research Personnel; Rest; Risk; Role; Sampling; Schedule; Sleep; Sleep Wake Cycle; Sleep disturbances; Structure of beta Cell of islet; Time; Triglycerides; Weight; Weight maintenance regimen; Weights and Measures; Woman; actigraphy; adiponectin; base; experimental study; ghrelin; improved; insulin sensitivity; intravenous glucose tolerance test; men; metabolic profile; obesity prevention; oxidation; peripheral blood; phase change; prevent; respiratory; response; subcutaneous

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.

项目摘要/摘要 定时饮食因其对体重调节的重大贡献而被认可。睡眠唤醒的破坏 从昼夜（白天）生活方式到延迟生活方式的循环会导致昼夜节律中断 和代谢功能障碍。在我们的R21（DK100787）中，我们研究了健康的正常体重成年人 跨界设计比较了在白天进行8周饮食的效果，而延迟时间表 持续的睡眠效果周期。我们的初步结果表明体重，呼吸商，树干脂肪，胰岛素， 白天时间表的总胆固醇和脂联素减少，而甘油三酸酯和葡萄糖增加 按时间表延迟。同样，在白天条件下，少年林的昼夜阶段也是先进的， 瘦素的延迟，但褪黑激素期与延迟状态保持不变。我们的结果提供了 第一个实验证据表明，白天饮食与延迟饮食相比会促进体重减轻和 燃料氧化和荷尔蒙标记的正曲线，并在正常情况下积极改变昼夜节律阶段 体重成年人。值得注意的是，这种饮食方式的代谢作用及其潜在的昼夜节律机制 在肥胖人群中的实验研究中尚未对其进行严格的研究。我们假设一个 与延迟的饮食时间表相比，持续的睡眠和活动水平相比，将减少 体重，改善新陈代谢特征并积极影响肥胖者的昼夜节律介导的反应， 降低发展代谢综合征和糖尿病的风险。 40位健康的男人和女人，21岁 - 50，BMI为30-50 kg/m2，将参加比较自由生活的随机跨界实验 白天饮食时间表（0800H-1900H）至延迟饮食时间表（1200H-2300H），具有可比的能量 大量营养素含量以及持续的睡眠效果周期（2300h-0700h）和运动（<30 min/d，<3 d/wk）。 我们的代谢厨房将在每种情况下为8周提供所有食物，并由2周的冲洗量隔开。协议 依从性将与食物日志密切监视 外面的食物，艺术学和每天的睡眠和运动自我报告。评估将进行4 时间，前后每8周的饮食状况，在此期间我们将测量：体重，身体成分， 呼吸商和休息能量消耗；胰岛素，葡萄糖，胆固醇，甘油三酸酯的禁食水平， 脂联素，非酯化脂肪酸和C反应性蛋白；和瘦素，生长素素，褪黑激素，葡萄糖的水平 和皮质醇和外周血的基因表达每4H（24h以上7倍）显示昼夜节律 饮食条件之间的相变。我们还将检查这些变化的基础机制 通过经常采样的静脉葡萄糖耐量测试来确定胰岛素敏感性，胰腺β 细胞功能，葡萄糖有效性和游离脂肪酸动力学以及通过皮下白脂肪 组织基因表达。这个多方面的项目将受益于调查人员的饮食专业知识 行为/体重管理，昼夜节律生物学，内分泌学和代谢以及生物信息学。