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

摘要 肥胖症正在达到流行的程度，影响着美国36%的成年人口。这个 肥胖治疗的一线是卡路里限制(CR)，尽管复发很常见。因此，替代方案 需要考虑CR的选项。 由于人类不断进食，每天延长禁食时间限制进食(Tre)改变了 肥胖症治疗的范例。在人类中，tre强制每天禁食(14-16小时)，只允许 在固定的每日进食窗口(~8至10小时)内摄取食物。通过在一项关于健康、 超重12周的人类，我们发现TrE减轻了体重和脂肪量，并对 进食窗口会导致更大的脂肪量和内脏脂肪的损失。作为动作记录仪-测量的身体 活动和睡眠指标没有改变，我们认为长时间的禁食是TRE的主要调节因素。 关联的更改。我们假设，自由摄取的TRE是CR的一种非常可行的替代方案 在减轻体重、脂肪质量和改善胰岛素敏感性方面，因为每天延长禁食时间会减少卡路里摄入量 并提高新陈代谢灵活性--在环境燃料暴露的情况下选择燃料的适应性。我们会 招募饮食窗口≥为14小时的肥胖、胰岛素抵抗的人，他们将被随机分为3人中的1人 1)自由进食8小时进食窗口组，2)减少15%热量摄入的CR组，3) 非TRE，自由摄取，12周。我们的具体目标包括：目标1：评估 自由摄取Tre对体重和体成分的影响。目标2：评估Tre与广告的效果 锂摄入量对热量平衡的影响。目的#3：评估自由摄取TrE对代谢灵活性的影响。 该项目的目标是研究长时间禁食在TRE相关代谢变化中的作用。 科学前提是与TRE相关的长时间禁食可以减少卡路里的摄取并增强 代谢灵活性-在环境燃料暴露的情况下选择燃料的适应性。因此，特雷将 加强禁食状态下的脂肪氧化和摄食状态下的碳水化合物氧化，以更具新陈代谢 在不延长禁食时间的情况下优于CR。其意义在于建立TRE作为一种实用的手段 在不延长禁食的情况下，大规模实施长时间禁食，是CR的可行替代方案， 从而改变肥胖症的治疗方法

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