Prolonged Daily Fasting As a Viable Alternative to Caloric Restriction in At-Risk Obese Humans

摘要 肥胖正在达到流行病的比例，影响了美国36%的成年人口。的 肥胖症治疗的第一线是热量限制（CR），尽管复发是常见的。因此，替代 需要考虑对CR的选择。 由于人类不断进食，通过限制时间进食（TRE）每日延长禁食改变了 肥胖症治疗的范例。在人类中，TRE通过仅允许 在固定的每日进食时间窗（约8至10小时）内进食。通过在健康的试点研究中实施TRE， 我们发现TRE减少了体重和脂肪量， 进食窗口导致更大的脂肪量和内脏脂肪损失。作为活动记录仪测量的物理 活动和睡眠指标没有改变，我们认为长时间禁食是TRE的主要介质， 相关的变化。我们假设TRE与自由摄入是CR的一种高度可行的替代方案 在减轻体重，脂肪量和改善胰岛素敏感性，因为每天延长禁食减少热量摄入 并增强代谢灵活性--给定环境燃料暴露的燃料选择的适应性。我们将 招募进食时间窗≥ 14小时的肥胖、胰岛素抵抗人群，将其随机分配至3组之一 组：1）TRE（8小时进食窗），随意摄入，2）CR，热量摄入减少15%，3） 非TRE，自由摄入12周。我们的具体目标包括：目标1：评估 TRE自由摄入对体重和身体组成影响。目标2：评估TRE与AD的效果 自由摄入对热量平衡的影响。目的3：评估TRE与随意摄入对代谢灵活性的影响。 该项目的目的是研究长期禁食在TRE-associated代谢变化中的作用。 科学前提是，与TRE相关的长时间禁食减少了热量摄入， 代谢灵活性-在环境燃料暴露条件下燃料选择的适应性。因此，TRE将 增强空腹状态下的脂肪氧化和进食状态下的碳水化合物氧化， 比不长期禁食的CR更有利。其意义在于将TRE作为一种实用的手段， 大规模延长禁食时间，是不延长禁食时间的CR的可行替代方案， 从而改变了肥胖症的治疗

ABSTRACT Obesity is reaching epidemic proportions, affecting 36% of the adult population in the United States. The first line of obesity treatment is caloric restriction (CR), although recidivism is common. Therefore, alternative options to CR need to be considered. As humans are constantly eating, daily prolonged fasting through time restricted eating (TRE) shifts the paradigm in obesity treatment. In humans, TRE imposes a daily fasting period (14-16 hours) by only allowing food intake during fixed daily eating window (~8 to 10 hours). By implementing TRE in a pilot study of healthy, overweight humans for 12 weeks, we found that TRE reduced weight and fat mass, with greater restriction of the eating window resulting in greater loss of fat mass and visceral fat. As actigraphy-measured physical activity and sleep measures did not change, we propose that prolonged fasting is the primary mediator of TRE- associated changes. We hypothesize that TRE with ad libitum intake presents a highly viable alternative to CR in reducing weight, fat mass and improving insulin sensitivity, as daily prolonged fasting reduces caloric intake and enhances metabolic flexibility—the adaptability of fuel selection given ambient fuel exposure. We will recruit obese, insulin-resistant humans with an eating window ≥14 hours, who will be randomized to 1 of 3 groups: 1) TRE (8 hour eating window) with ad libitum intake, 2) CR with 15% reduction of caloric intake, 3) non-TRE with ad libitum intake for 12 weeks. Our specific aims include the following: Aim#1: Evaluate the effect of TRE with ad libitum intake on weight and body composition. Aim#2: Assess the effect of TRE with ad libitum intake on caloric balance. Aim#3: Assess the effect of TRE with ad libitum intake on metabolic flexibility. This project’s objective is to examine the role of prolonged fasting in TRE-associated metabolic changes. The scientific premise is that prolonged fasting associated with TRE reduces caloric intake and enhances metabolic flexibility—the adaptability of fuel selection given ambient fuel exposure. Therefore, TRE will enhance fat oxidation in the fasting state and carbohydrate oxidation in the fed state, to be more metabolically advantageous than CR without prolonged fasting. The significance is establishing TRE as a practical means of implementing prolonged fasting on a large scale and a viable alternative to CR without prolonged fasting, thereby transforming the treatment of obesity