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寿命，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) 来监测饮食依从性并遵守 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。