Environmental Obesogens and Weight Change in the POUNDS LOST Trial

项目总结/摘要 环境化学物质在人类肥胖病因学中的作用已经被证实， 越来越欣赏。在本提案中，我们的目标是评估多环芳烃（PAHs）， 杂环芳族胺（哈斯）与人类受试者体重变化的关系。的致癌作用 这些无处不在的污染物是有据可查的，新出现的证据表明，这些化学物质 还可能通过发挥雌激素效应等途径破坏内分泌功能。有限的人力 证据，通常来自横截面研究，也支持这一假设，即这些化学品是潜在的 虽然需要前瞻性数据来证实这些化学物质之间的联系， 和体重的过度增加。我们建议1）检测24小时尿液中多环芳烃和哈斯的排泄 POUNDS Lost试验中与能量限制引起的短期体重减轻相关的样本; 2） 评估在减肥期间这些化学物质的尿排泄变化是否可预测体重 在POUNDS Lost试验中重新获得; 3）调查24小时内这些化学物质水平之间的关联 参加护士健康研究II的女性和男性的尿样和长期体重变化 （NHSII）和年轻人冠状动脉风险发展（CARDIA）。此外，根据路径 通过这两组化学品可以协同放大彼此的有害影响，我们 还将研究多环芳烃和哈斯之间的潜在相互作用对体重减轻，体重恢复，和长期 研究中的体重变化。为了确保高质量的科学数据，我们精心设计了我们的建议， 问题研究在POUNDS Lost、NHSII和CARDIA研究中，我们将对24小时尿液中的PAH和哈斯进行定量 样品，以大大提高尿液测量随时间的再现性。在这三项研究中， 已收集了体重和与体重变化相关的许多其他变量 在随访期间重复进行，以便进行全面的纵向数据分析。我们将限制 研究对象为基本健康、不吸烟的人，以尽量减少慢性病和吸烟的影响 关于利益的关联。为了实现这些目标，我们组建了一支经验丰富的研究团队 在环境健康，肥胖流行病学，生物标志物研究， 生物统计学和生物信息学，以及毒理学。我们将与中心的知名实验室合作， 疾病控制和预防，以测量24小时尿样中的PAH和HAA水平。数据 从这个项目产生的将大大加深我们对潜在的，肥胖的影响， 人群中的多环芳烃和哈斯。此外，这项拟议研究的证据也将有助于 制定政策或建议，以减少对这些化学品的接触， 人体健康

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.