Time restricted feeding versus daily calorie restriction: Effect on body weight, metabolic risk, and the gut microbiome

项目总结/摘要 背景：近年来，时间限制喂养（TRF）越来越受欢迎。TRF通常 包括将进食时间限制在6-8小时，并在一天的其余时间禁食。在吃饭的时候 窗口，个人不需要监测能量摄入。扶轮基金会如此受欢迎的原因之一是 因为它不需要个人计算卡路里来减肥。扶轮基金会的这个特点可能 大大提高长期坚持这种饮食，反过来又产生持久的体重控制。尽管它的成长 由于TRF的普及，只有四项人体试验研究了TRF对体重的影响。虽然这些初步 研究显示TRF作为减肥干预措施的前景，这些先前的试验受到持续时间短的限制 (2-4月），缺乏对照组，并且没有与传统节食（每日卡路里限制; CR）进行比较。 我们最近进行了一项初步研究，比较6小时TRF与每日CR在成人中的减肥效果 肥胖和糖尿病前期我们的研究结果显示，扶轮基金会产生了更大的坚持，能量限制， 3个月内体重减轻（-5%）对比CR（-3%）。TRF也产生更明显的胰岛素减少 抵抗力、血压和氧化应激，与CR相比。然而，仍然未知的是， 扶轮基金会的这些改善在较长时期（12个月）内会变得更显著，如果 TRF可以帮助个人保持体重减轻和代谢疾病的持续减少 风险TRF对身体上级作用的机制（微生物组、食欲、肠道肽） 体重和坚持，也仍然未知。方法：一项为期12个月的随机、对照、平行组试验， 分为：（1）6个月的减肥期;（2）6个月的维持期，将实施。成年人 肥胖和糖尿病前期患者（n = 120）将被随机分为3组之一：（1）6 h-TRF（n = 40）自由进食 每天下午1-7点进食，每天下午7- 1点禁食;（2）CR（n = 40），每天限制25%能量;或（3）对照（n = 40），每日随意进食。假设：本提案将测试以下假设：（Hyp 1） 与CR相比，TRF组将更坚持干预，这将产生更大的能量 限制、减肥和维持减肥;（Hyp 2）扶轮基金会组将经历更大的 改善胰岛素敏感性（通过钳夹测量）、血脂、血压、炎症和 氧化应激对CR;（Hyp 3）TRF组将产生更大的组合物改善， 结构和肠道微生物群的代谢活性，以及食欲和肠道肽，与CR相比， 与上级粘附性和体重减轻有关。意义：这项研究将首次表明扶轮基金会 可以作为传统节食（即每日卡路里限制）的替代方案， 管理这项研究还将表明，TRF可以作为一种有效的非药物治疗， 改善胰岛素敏感性和降低代谢疾病风险。的 还将阐明TRF有益作用的基础机制（肠道微生物组和食欲）。

Project Summary/ Abstract Background: Time restricted feeding (TRF) has greatly increased in popularity in recent years. TRF typically involves confining the eating window to 6-8 h, and fasting for the remaining hours of the day. During the eating window, individuals are not required to monitor energy intake. One of the reasons why TRF is so popular, is because it does not require individuals to count calories in order to lose weight. This feature of TRF may greatly improve long-term adherence to this diet, and in turn produce lasting weight control. Despite its growing popularity, only four human trials have examined the effect of TRF on body weight. While these preliminary studies show promise for TRF as a weight loss intervention, these previous trials are limited by short duration (2-4 months), lack of a control group, and no comparison to traditional dieting (daily calorie restriction; CR). We recently conducted a pilot study to compare the weight loss efficacy of 6-h TRF versus daily CR in adults with obesity and prediabetes. Our findings show that TRF produced greater adherence, energy restriction, and weight loss (-5%) versus CR (-3%) over 3 months. TRF also produced more pronounced reductions in insulin resistance, blood pressure, and oxidative stress, versus CR. What remains unknown, however, is whether these improvements by TRF would become more pronounced over longer periods of time (12-months), and if TRF can be implemented to help individuals maintain weight loss and sustain reductions in metabolic disease risk. The mechanisms (microbiome, appetite, gut peptides) that underlie the superior effects of TRF on body weight and adherence, also remain unknown. Methods: A 12-month randomized, controlled, parallel-arm trial, divided into: (1) 6-month weight loss period; and (2) 6-month maintenance period, will be implemented. Adults with obesity and prediabetes (n = 120) will be randomized to 1 of 3 groups: (1) 6h-TRF (n = 40) ad libitum food intake from 1-7 pm, fasting from 7-1pm daily, (2) CR (n = 40), 25% energy restriction daily; or 3) control (n = 40), ad libitum food intake daily. Hypotheses: The present proposal will test the following hypotheses: (Hyp1) The TRF group will be more adherent with the intervention versus CR, which will result in greater energy restriction, weight loss and weight loss maintenance; (Hyp2) The TRF group will experience greater improvements in insulin sensitivity (measured by clamp), plasma lipids, blood pressure, inflammation, and oxidative stress versus CR; (Hyp3) The TRF group will produce greater improvements in the composition, structure, and metabolic activity of the gut microbiota, as well as in appetite and gut peptides, vs CR, which will be related to superior adherence and weight loss. Significance: This study will be the first to show that TRF can be implemented as an alternative to traditional dieting (i.e. daily calorie restriction) for long-term weight management. This study will also show that TRF can be used as an effective non-pharmacological therapy to improve insulin sensitivity and decrease metabolic disease risk in individuals with prediabetes and obesity. The mechanisms (gut microbiome and appetite) that underlie the beneficial effects of TRF will also be elucidated.