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

间歇性能量限制对腹内脂肪和肠道微生物组的影响：随机试验

基本信息

批准号：
10304526
负责人：
CAROL J BOUSHEY
金额：
$ 110.48万
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-22 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10304526
关键词：
Abdomen Accelerometer Adherence Adult Anthropometry Asian Pacific Islander Asians Behavioral Biological Biological Markers Blood Body Weight Body Weight decreased Body fat Body mass index Breast Cancer Risk Factor Central obesity Clinical Cohort Studies Conduct Clinical Trials Consultations Custom DASH diet Data Diet Diet Monitoring Dietary Intervention Dietary Practices Dietary intake Dietitian Dual-Energy X-Ray Absorptiometry Eating Effectiveness Ethnic Origin Ethnic group Etiology Expectancy Fatty acid glycerol esters Food Frequencies Future General Population Hawaii Health Heart Hip region structure IGFBP3 gene Insulin Insulin-Like Growth Factor I Intervention Interview Intra-abdominal Lead Leptin Liver Longevity Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of liver Measurement Measures Mediator of activation protein Mediterranean Diet Metabolic Metagenomics Modification Native Hawaiian Obesity Obesity associated cancer Outcome Pacific Island Americans Participant Phenotype Physical activity Play Population Population Heterogeneity Problem Solving Production Protocols documentation Psychological reinforcement Questionnaires Randomized Recommendation Reporting Research Risk Risk Factors Role SHBG gene Safety Self Efficacy Social support Stimulus Structure Telephone Testing Time Translational Research Visceral Visceral fat Woman Work abdominal fat actigraphy active comparator adiponectin base blood-based biomarker cancer biomarkers cancer risk cohort dietary restriction dissemination research efficacy outcomes ethnic difference ethnic diversity good diet group intervention gut microbiome gut microbiota healthy lifestyle healthy weight improved intervention participants lipid metabolism malignant breast neoplasm men microbial microbiome composition middle age multi-ethnic new technology non-alcoholic fatty liver disease obesity risk post intervention psychosocial racial and ethnic racial and ethnic disparities randomized trial recruit safety and feasibility systemic inflammatory response

项目摘要

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.

项目概要/摘要间歇性能量限制 (IER) 被认为比每日 ER (DER) 具有重要优势产生持续的体重减轻并降低癌症风险。虽然IER已经在普遍推广人口为了改善健康和长寿，迫切需要严格执行的支持性证据随机试验。我们提议进行一项为期六个月的随机试验，以证明 IER 相对于 DER 的优越性减少异位脂肪和总脂肪量，并改善癌症相关生物标志物和肠道微生物组功能。我们之前的工作强烈表明，异位脂肪独立于总肥胖，发挥着重要作用。在肥胖相关癌症的病因学和种族/民族差异中发挥重要作用。我们报道了体重指数 (BMI) 与患病风险之间的关联强度存在显着的种族/民族差异多种族队列 (MEC) 中与肥胖相关的癌症。我们观察到相应的差异最近的一项基于 MRI 的研究显示，同一五个种族群体内脏和肝脏脂肪积累的倾向并证明了基于生物标志物的内脏脂肪评分与乳房事件之间存在独立关联 MEC 中的癌症。此外，我们还结合地中海饮食模式调整了 IER 方案（IER+MED）并证明了其可行性、安全性和比主动比较器（心脏- 健康的 DER 方法）减少总肥胖和异位肥胖并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，受试者为 60 名患有内脏肥胖的亚洲各族中年人。我们现在提出健康饮食和生活方式研究 II，这是一项针对 IER+MED 与 MED/DER 的为期 24 周的随机试验 260 名东亚、太平洋岛民或白人中年欧胡岛成年人中，增值税高于人口中位数。干预措施将通过 16 次有针对性的定制咨询来实施研究营养师，将包括 IER+MED（IER 是连续两天限制 70% 的能量，一周中其他五天的能量充足的 MED 饮食）或每日能量限制为 20% 的 MED （医学/德尔）。营养师将使用移动食品记录 (mFR) 和遵守在整个干预过程中使用访谈和体动记录来推荐常见的身体活动建议。我们将比较 IER+MED 与 MED/DER 的 MRI 测量内脏和肝脏脂肪以及 DXA 测量总脂肪的减少情况肥胖（目标 1）以及改善癌症相关生物标志物（IGF-1、IGFBP3、胰岛素、HOMA-IR、瘦素、脂联素、S HBG、hsCRP）和微生物代谢产物产生的粪便宏基因组标记（目标 2）。我们还将调查遵守规定 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剧集（目标 3）。这项研究将为 IER 在降低癌症相关风险因素方面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，以降低美国不同人群的癌症风险。