Circadian Misalignment and Energy Metabolism

描述（由申请人提供）：昼夜节律计时和代谢生理学的相互作用代表了生物医学研究的新前沿。关于人类体重增加的研究主要集中在大量营养素摄入和能量消耗上，后者主要通过体力活动来理解和治疗超重和肥胖。来自动物模型的新证据表明，昼夜节律生理学影响体重增加，包括在时钟基因突变体中观察到肥胖，以及最近的发现，与正常清醒期间相同数量的食物摄入相比，限制小鼠习惯性睡眠时间的食物摄入会导致体重增加。我们建议确定这些小鼠模型的发现是否适用于人类。为此，我们设计了一项探索性的临床和转化研究中心（CTRC）研究，该研究使用全房间热量测定法来确定将大部分食物摄入限制在生物夜间如何影响人类的能量代谢。在夜间进食在具有长工作时间的工作时间表中以及在夜间时间期间的工作操作中是常见的（例如，健康护理、紧急响应、安全人员）和昼夜睡眠障碍，包括但不限于 工作和时差综合症。夜间进食障碍也是新认识到的可能导致肥胖的疾病。该项目通过测试以下特定假设来解决NIH PA编号：09-124“肥胖症的探索性/发展性临床研究赠款”中概述的几个主题：i）昼夜节律失调将导致脂肪氧化减少-一种可能导致体重增加的生理状态。这项研究工作是对PA-09-124的响应，因为它将评估夜间进食的行为表型如何增加肥胖的风险，并将有助于将这种行为确定为超重和肥胖的可改变决定因素。

DESCRIPTION (provided by applicant): The interplay of circadian timing and metabolic physiology represents a new frontier in biomedical research. Research on weight gain in humans has focused primarily on macronutrient intake and energy expenditure, the latter predominantly through physical activity, to understand and treat overweight and obesity. Emerging evidence from animal models indicates that circadian physiology impacts weight gain, including the observation of obesity in clock gene mutants and most recently the finding that food intake restricted to the habitual sleep time of mice leads to weight gain as compared to the same amount of food intake during the normal wake episode. We propose to determine if findings from these mouse models translate to humans. To do so, we have designed an exploratory Clinical and Translational Research Center (CTRC) study that uses whole room calorimetry to determine how restricting the majority of food intake to the biological night impacts energy metabolism in humans. Eating at night is common in work schedules with long work hours and with work operations during the nighttime hours (e.g., health care, emergency response, security personnel) and in circadian sleep disorders including, but not limited to, shift work and jet lag disorder. Night eating disorders are also newly recognized conditions that may contribute to obesity. The project addresses several themes outlined in NIH PA NUMBER: 09-124 "Exploratory/Developmental Clinical Research Grants in Obesity" by testing the following specific hypothesis: i) circadian misalignment will lead to reduced fat oxidation-a physiological state that could contribute to weight gain. This research effort is responsive to PA-09-124 as it will assess how a behavioral phenotype of eating at night increases risk for obesity and will contribute to identification of this behavior as a modifiable determinant of overweight and obesity.