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

项目摘要/摘要 背景：近年来，限时喂养(TRF)的普及程度大大提高。扶轮基金会通常 包括将进食时间限制在6-8小时，并在一天中的其余几个小时禁食。在吃的时候 窗口，个人不需要监测能量摄入量。扶轮基金会如此受欢迎的原因之一是 因为它不需要个人为了减肥而计算卡路里。TRF的这一功能可以 大大改善对这种饮食的长期坚持，进而产生持久的体重控制。尽管它在不断增长 尽管很受欢迎，但只有四项人体试验研究了TRF对体重的影响。虽然这些初步的 研究表明，TRF作为一种减肥干预措施很有希望，这些先前的试验受到持续时间较短的限制 (2-4个月)，没有对照组，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，以比较6小时TRF和每日CR在成人中的减肥效果 患有肥胖症和糖尿病前期。我们的发现表明，TRF产生了更大的依从性、能量限制和 3个月内体重减轻(-5%)与CR(-3%)相比。TRF也产生了更显著的胰岛素减少。 抵抗力、血压和氧化应激，与CR相比。然而，目前尚不清楚的是， 扶轮基金会的这些改进将在更长的时间段(12个月)变得更加明显，如果 可以实施TRF来帮助个人保持体重减轻和代谢性疾病的减少 风险。TRF对人体产生优越作用的机制(微生物群、食欲、肠肽) 重量和粘附性，也是未知的。方法：一项为期12个月的随机对照平行对照试验， 分为：(1)6个月的减肥期；(2)6个月的维护期，将执行。成虫 有肥胖和糖尿病前期的患者(n=120)将被随机分为3组：(1)6h-TRF(n=40)随意饮食 摄入时间为下午1-7点，禁食时间为每天晚上7-1点；(2)CR组(n=40)，每天限制25%的能量摄入；或(3)对照组(n= 40)，每天自由进食。假设：目前的建议将检验以下假设：(Hyp1) 与CR相比，TRF组对干预的依从性更强，这将导致更大的能量 限制、减肥和减肥维持；(Hyp2)TRF组将经历更多 改善胰岛素敏感性(通过钳夹测量)、血脂、血压、炎症和 氧化应激与CR；(Hyp3)TRF组将在成分上产生更大的改善， 肠道微生物区系的结构和代谢活性，以及食欲和肠肽，与CR相比，这将 与超强的坚持和减肥有关。意义：这项研究将首次表明扶轮基金会 可以作为长期体重的传统节食(即每日卡路里限制)的替代方案 管理层。这项研究还将表明，TRF可以作为一种有效的非药物疗法用于治疗 改善糖尿病前期和肥胖者的胰岛素敏感性，降低代谢性疾病风险。这个 TRF有益作用的机制(肠道微生物群和食欲)也将被阐明。

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.