Environmental Obesogens and Weight Change in the POUNDS LOST Trial

POUNDS LOST 试验中的环境致肥胖因素和体重变化

• 批准号: 10596998
• 负责人: Qi Sun
• 金额: $ 59.63万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596998
• 关键词: Adipose tissue; Adult; Animal Experiments; Animals; Aromatic Polycyclic Hydrocarbons; Basal metabolic rate; Basic Science; Binding; Bioinformatics; Biological Markers; Biometry; Body Weight; Body Weight Changes; Body Weight decreased; Body fat; Centers for Disease Control and Prevention (U.S.); Chemicals; Chronic Disease; Collaborations; Coronary Artery Risk Development in Young Adults Study; Critical Pathways; Cross-Sectional Studies; Data; Data Analyses; Diet; Endocrine disruption; Ensure; Environmental Health; Environmental Pollutants; Epidemiology; Estrogen Receptors; Etiology; Excretory function; Exposure to; Food; Gene Expression; Generations; Genetic; Grant; Health; Hour; Human; Individual; Inflammation; Intake; Intervention; Investigation; Knowledge; Leptin; Light; Longitudinal, observational study; Measurement; Measures; Meat; Mediating; Nurses' Health Study; Obesity; Obesity Epidemic; Outcome; Participant; Pathway interactions; Peroxisome Proliferator-Activated Receptors; Physical activity; Policies; Poly-fluoroalkyl substances; Population; Prevalence; Process; Property; Prospective Studies; Proteins; Recommendation; Reproducibility; Research; Research Design; Resources; Risk; Risk Factors; Role; Sampling; Smoking; Source; Thyroid Hormones; Time; Toxicology; Urine; Weight; Weight Gain; Woman; anthropogenesis; bisphenol A; carcinogenicity; chemical group; design; development policy; dietary; dietary approach; environmental chemical; estrogenic; excessive weight gain; experience; follow-up; heterocyclic aromatic amines; human data; human subject; improved; interest; leptin receptor; men; non-smoking; novel; novel strategies; obesity prevention; obesity risk; obesogen; obesogenic; pollutant; prospective; rapid weight gain; trend; urinary; waist circumference; weight maintenance

Project Summary/Abstract The role of environmental chemicals known as obesogens in the etiology of human adiposity has been increasingly appreciated. In this proposal, we aim to evaluate polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs) in relation to weight change in human subjects. The carcinogenic effects of these ubiquitous pollutants are well-documented, and emerging evidence suggests that these chemicals may also disrupt endocrine functions through exerting estrogenic effects and other pathways. Limited human evidence, often from cross-sectional studies, also supports the hypothesis that these chemicals are potential obesogens, although prospective data are needed to substantiate the associations between these chemicals and excess weight gain in humans. We propose to 1) examine excretion of PAHs and HAAs in 24-hour urine samples in relation to short-term weight loss induced by energy restriction in the POUNDS Lost trial; 2) evaluate whether changes in urinary excretion of these chemicals during weight loss period predict weight regain in the POUNDS Lost trial; and 3) investigate associations between levels of these chemicals in 24-hour urine samples and long-term weight change in women and men participating in the Nurses' Health Study II (NHSII) and Coronary Artery Risk Development in Young Adults (CARDIA). In addition, in light of the pathways through which these two groups of chemicals may synergistically amplify each other's detrimental effects, we will also examine potential interactions between PAHs and HAAs on weight loss, weight regain, and long-term weight change in the studies. To ensure high quality scientific data, we have carefully designed our proposed studies. In the POUNDS Lost, NHSII, and CARDIA studies, we will quantify PAHs and HAAs in 24-hour urine samples to substantially improve the reproducibility of urinary measurements over time. In all three studies, body weight and a multitude of other variables that are related with body weight change have been collected repeatedly during follow-up, allowing for comprehensive, longitudinal data analyses. We will restrict the research to largely healthy, non-smoking individuals to minimize the impact of chronic diseases and smoking on the associations of interest. To accomplish the aims, we have assembled an experienced research team with interdisciplinary expertise in the fields of environmental health, obesity epidemiology, biomarker research, biostatistics and bioinformatics, and toxicology. We will collaborate with highly reputable labs at the Centers for Disease Control and Prevention to measure PAH and HAA levels in 24-hour urine samples. Data to be generated from this project will substantially deepen our understanding of the potential, obesogenic effects of PAHs and HAAs in human populations. Moreover, evidence from this proposed research will also aid in the development of policies or recommendations toward reducing exposures to these chemicals and improving human health.

项目摘要/摘要 环境化学物质在人类肥胖病学中的作用一直是 越来越感谢。在此提案中，我们旨在评估多环芳烃（PAHS）和 与人类受试者体重变化有关的杂环芳香胺（HAA）。致癌作用 这些无处不在的污染物有充分的文献记录，新兴的证据表明这些化学物质 还可能通过发挥雌激素作用和其他途径来破坏内分泌功能。有限的人 通常来自横断面研究的证据也支持以下假设。 服役，尽管需要前瞻性数据来证实这些化学物质之间的关联 和人类的体重增加。我们建议1）检查24小时尿液中PAH和HAA的排泄 与磅损失试验中能量限制引起的短期体重减轻有关的样本； 2） 评估减肥期间这些化学物质的尿排泄的变化是否预测重量 重新获得失去的审判； 3）研究这些化学物质水平在24小时内的关联 参加护士健康研究的男性和男性的尿液样本和长期体重变化II （NHSII）和年轻人的冠状动脉风险发展（Cardia）。另外，鉴于路径 通过这两组化学物质可以协同扩大彼此的有害影响，我们 还将检查PAHS与HAA之间的潜在相互作用，以减轻体重，体重恢复和长期 研究的体重变化。为了确保高质量的科学数据，我们精心设计了我们的建议 研究。在损失，NHSII和Cardia研究中，我们将在24小时尿液中量化PAHS和HAAS 样品可以实质上提高尿测量的可重复性。在所有三项研究中， 已经收集了体重和许多与体重变化相关的其他变量 在随访期间反复进行，允许进行全面的纵向数据分析。我们将限制 研究主要是健康，无吸烟的人，以最大程度地减少慢性疾病和吸烟的影响 关于感兴趣的协会。为了实现目标，我们组建了一个经验丰富的研究团队 具有跨学科的专业知识，在环境健康领域，肥胖流行病学，生物标志物研究中， 生物统计学和生物信息学和毒理学。我们将与中心备受信誉的实验室合作 疾病控制和预防以测量24小时尿液样品中的PAH和HAA水平。数据 该项目产生的将大大加深我们对潜在的肥胖作用的理解 人口中的PAH和HAA。此外，这项拟议研究的证据也将有助于 制定政策或建议减少对这些化学物质的暴露并改善的建议 人类健康。