Effects of Intermittent Energy Restriction on Intra-Abdominal Fat and the Gut Microbiome: A Randomized Trial

项目概要/摘要 间歇性能量限制（IER）已被认为比每日ER（DER）具有重要的优势， 持续减肥和降低癌症风险。虽然IER已经在普遍推广， 为了改善人口的健康和长寿，迫切需要从严格的 随机试验我们提出了一项为期6个月的随机试验，以证明IER优于DER， 减少异位脂肪和总脂肪量，改善癌症相关生物标志物和肠道微生物组 功能协调发展的我们以前的工作强烈地表明，异位脂肪，独立于总的肥胖，发挥了重要作用。 在肥胖相关癌症的病因学和种族/民族差异中的重要作用。我们报道 在体重指数（BMI）和肥胖风险之间的关联强度方面存在显著的种族/民族差异。 多种族队列（MEC）中的肥胖相关癌症。我们观察到相应的差异， 在最近的一项基于MRI的研究中， 并证明了基于生物标志物的内脏脂肪评分与乳腺癌发病率的独立相关性。 MEC中的癌症此外，我们采用了IER协议结合地中海饮食模式， (IER+MED），并证明了其可行性、安全性和优于活性对照药物（心脏- 健康的DER方法）减少总脂肪和异位脂肪，改善有益的肠道微生物组功能 在一项为期12周的随机试验中，60名患有内脏肥胖的亚洲不同种族的中年人。 我们现在提出健康饮食和生活方式研究II，一项为期24周的IER+MED与MED/DER的随机试验 在260名东亚、太平洋岛民或白色种族的中年欧裔成年人中， 人口中位数。干预措施将通过16次有重点和定制的协商进行， 研究营养师，将包括IER+MED（IER是连续两天70%的能量限制， 一周中其他五天的能量充足的MED饮食）或MED每日能量限制为20% (MED/DER）。营养师将使用移动的食物记录（mFR）监测饮食依从性， 在整个干预过程中，使用访谈和活动记录仪推荐常见的体力活动。我们将 比较IER+MED与MED/DER的MRI测量的内脏和肝脏脂肪以及DXA测量的总脂肪减少 肥胖症（目的1）和癌症相关生物标志物（IGF-1，IGFBP 3，胰岛素，HOMA-IR，瘦素， 脂联素、S HBG、hsCRP）和微生物代谢产物的粪便宏基因组标志物（目的2）。我们 还将调查遵守规定的IER的行为预测因素，包括心理社会措施 自我效能和结果预期，以及基于进食时间和频率的饮食模式 目标3）。这项研究将为IER降低癌症相关风险因素提供可靠的有效性数据 并为未来的转化和传播研究提供信息，以降低美国各种人群的癌症风险。

PROJECT SUMMARY/ABSTRACT Intermittent energy restriction (IER) has been suggested to have important advantages over daily ER (DER) in producing sustained weight loss and reducing cancer risk. While IER is already being promoted in the general population to improve health and longevity, supportive evidence is urgently needed from rigorously conducted randomized trials. We propose a six-month randomized trial to demonstrate the superiority of IER over DER in reducing ectopic fat and total fat mass, and in improving cancer-related biomarkers and gut microbiome functions. Our previous work strongly suggests that ectopic fat, independently of total adiposity, plays an important role in the etiology of, and in the racial/ethnic disparities in, obesity-related cancers. We reported striking racial/ethnic differences in the strength of the association between body mass index (BMI) and risk of obesity-related cancers in the Multiethnic Cohort (MEC). We observed corresponding disparities in the propensity to accumulate visceral and liver fat among the same five ethnic groups in a recent MRI-based study and demonstrated an independent association of a robust biomarker-based visceral fat score with incident breast cancer in MEC. Additionally, we adapted an IER protocol combined with a Mediterranean dietary pattern (IER+MED) and demonstrated its feasibility, safety and greater efficacy over an active comparator (a heart- healthy DER approach) in reducing total and ectopic adiposity and improving beneficial gut microbiome functions in a 12-week randomized trial among 60 middle-aged adults of various Asian ethnicities with visceral obesity. We now propose the Healthy Diet and Lifestyle Study II, a 24-week randomized trial of IER+MED vs. MED/DER among 260 middle-aged Oahu adults of East-Asian, Pacific Islander or white ethnicity with VAT greater than the population median. The intervention will be delivered through 16 focused and customized consultations with research dietitians and will consist of an IER+MED (IER is 70% energy restriction on two consecutive days and a euenergetic MED diet for the other five days of the week) or the MED with a 20% daily energy restriction (MED/DER). Dietitians will monitor dietary compliance using the mobile food record (mFR) and compliance to a common physical activity recommendation using interviews and actigraphy throughout the intervention. We will compare IER+MED vs. MED/DER for reduction in MRI-measured visceral and liver fat and DXA-measured total adiposity (Aim 1) and for improvement in cancer-related biomarkers (IGF-1, IGFBP3, insulin, HOMA-IR, leptin, adiponectin, S HBG, hsCRP) and fecal metagenomic markers of microbial metabolite production (Aim 2). We will also investigate behavioral predictors of adherence to the prescribed IER, including psychosocial measures of self-efficacy and outcome expectancies, and dietary patterns based on timing and frequency of eating episodes (Aim 3). This study will provide robust effectiveness data for IER on lowering cancer related risk factors and inform future translational and dissemination research to reduce cancer risk in various US populations.