Environmental Obesogens and Weight Change in the POUNDS LOST Trial

项目摘要/摘要 环境化学物质在人类肥胖症的病因中所起的作用 越来越受人赞赏。在这项提案中，我们旨在评估多环芳烃(PAHs)和 杂环芳胺(HAAs)与人体体重变化的关系。致癌作用 这些无处不在的污染物都有很好的记录，而且新出现的证据表明，这些化学物质 也可能通过发挥雌激素效应和其他途径扰乱内分泌功能。有限的人类 通常来自横断面研究的证据也支持这样的假设，即这些化学物质是潜在的 致肥胖症，尽管需要前瞻性数据来证实这些化学物质之间的关联 以及人类的超重增加。我们建议1)检测24小时尿中多环芳烃和杂环芳烃的排泄量 磅减少试验中与能量限制导致的短期体重下降有关的样本；2) 评估减肥期尿液中这些化学物质的排泄变化是否能预测体重 在减重试验中恢复；以及3)调查24小时内这些化学物质水平之间的关系 参加护士健康研究II的男女的尿样和长期体重变化 (NHSII)和青年冠状动脉风险发展(CARDIA)。此外，根据这些路径， 通过这两组化学物质可以协同放大彼此的有害影响，我们 还将研究PAHs和HAAs在减肥、体重回升和长期减肥方面的潜在相互作用 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 学习。在减重、NHSII和CARDIA研究中，我们将量化24小时尿中的PAHs和HAAs 随着时间的推移，可以显著提高尿液测量的重复性。在所有三项研究中， 收集了体重和许多其他与体重变化有关的变量 在跟踪期间反复进行，以便进行全面、纵向的数据分析。我们将限制 针对基本健康、不吸烟的人进行研究，将慢性病和吸烟的影响降至最低 利益相关者之间的联系。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、生物标记物研究、 生物统计学和生物信息学，以及毒理学。我们将与该中心的声誉良好的实验室合作 疾病控制和预防检测24小时尿样中的PAH和HAA水平。待处理的数据 从这个项目中产生的结果将大大加深我们对 人口中的多环芳烃和杂环芳烃。此外，这项拟议研究的证据也将有助于 制定政策或建议，以减少接触这些化学品并改善 人类健康。

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.