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

• 批准号: 10700063
• 负责人: CAROL J BOUSHEY
• 金额: $ 111.05万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 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/10700063
• 关键词: Abdomen; Accelerometer; Adherence; Adult; Anthropometry; Asian; Behavior assessment; 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; DASH diet; Data; Diet; Diet Monitoring; Dietary Intervention; Dietary Practices; Dietary intake; Dietitian; Disparity; Dual-Energy X-Ray Absorptiometry; East Asian; Eating; Effectiveness; Ethnic Origin; Ethnic Population; 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; Leptin; Liver; Longevity; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Measurement; Measures; Mediator; Mediterranean Diet; Metabolic; Metagenomics; Modification; Native Hawaiian or Other Pacific Islander; Obesity; Obesity associated cancer; Outcome; Pacific Islander; 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; behavior prediction; blood-based biomarker; cancer risk; cohort; dietary restriction; dissemination research; ethnic difference; ethnic disparity; ethnic diversity; good diet; group intervention; gut microbiome; gut microbiota; healthy lifestyle; healthy weight; improved; lipid metabolism; malignant breast neoplasm; microbial; microbiome composition; middle age; multi-ethnic; new technology; non-alcoholic fatty liver disease; obesity risk; post intervention; psychosocial; racial difference; racial disparity; racial population; randomized trial; recruit; safety and feasibility; systemic inflammatory response

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.

项目摘要/摘要 建议与每日ER（der）具有重要优势（IER） 产生持续的体重减轻并降低癌症风险。虽然IER已经被晋升为一般 人口以改善健康和寿命，严格进行迫切需要支持证据 随机试验。我们提出了一个为期六个月的随机试验，以证明IER优于DER 减少异位脂肪和总脂肪质量，并改善与癌症相关的生物标志物和肠道微生物组 功能。我们以前的工作强烈表明，异位脂肪独立于完全肥胖，发挥了作用 在与肥胖有关的癌症的病因和种族/种族差异的病因和种族差异中的重要作用。我们报道 在体重指数（BMI）之间的关联强度和风险的风险 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 在最近的一项基于MRI的研究中 并证明了强大的基于生物标志物的内脏脂肪评分与事件乳房的独立关联 MEC的癌症。此外，我们改编了IER方案与地中海饮食模式相结合 （IER+MED），并证明了其可行性，安全性和更大的功效（心脏 健康的方法）降低总肥胖和改善有益肠道微生物组函数的方法 在60名具有内脏肥胖的亚洲种族的中年成年人中进行了为期12周的随机试验。 现在，我们提出了健康的饮食和生活方式研究II，这是一项24周的IER+MED与MED/DER的随机试验 在东亚，太平洋岛民的260名中年中年瓦胡岛成年人中，增值税大于 人口中位数。干预将通过16次重点和自定义的咨询来进行 研究营养师，将由IER+MED组成（IER连续两天为70％的能量限制，并且 一周中其他五天的Euenergetic Med Diet）或每日能量限制为20％的MED （MED/DER）。营养师将使用移动食品记录（MFR）监测饮食的依从性，并遵守 在整个干预过程中，使用访谈和行为的常见体育锻炼建议。我们将 比较IER+MED与MED/DER，以减少MRI测量的内脏和肝脏脂肪以及DXA测量的总计 肥胖（AIM 1）和改善与癌症相关的生物标志物（IGF-1，IGFBP3，胰岛素，HOMA-IR，Leptin，leptin， 脂联素，S HBG，HSCRP）和微生物代谢物生产的粪便元基因组标志物（AIM 2）。我们 还将调查遵守规定IER的行为预测指标，包括社会心理措施 基于时间和饮食频率的自我效能和预期结果以及饮食模式 情节（目标3）。这项研究将为IER提供强大的有效性数据，以降低癌症相关的危险因素 并告知未来的翻译和传播研究，以降低美国各个人群的癌症风险。