Environmental Obesogens and Weight Change in the POUNDS LOST Trial

描述（由申请人提供）：拟开展的研究将从一个新的角度探讨人类肥胖和超重的发病机制——可疑工业化学品可能产生的影响，这是一项前瞻性研究。虽然营养过剩和久坐不动的生活方式是公认的肥胖风险因素，但其他潜在的肥胖因素的作用也很可能需要阐明。被称为“致肥源”的环境化学物质可能会扰乱体重调节。全氟化合物（pfc）是一种无处不在的持久性化学物质，会干扰动物模型中的能量稳态。然而，由于全氟化合物的物种特异性毒性动力学、组织分布和作用机制，动物数据与人类的相关性尚不确定。主要来自横断面研究的人类证据在很大程度上与pfc与较高体重相关的假设一致，但缺乏前瞻性数据排除了任何因果推断。因此，研究人员将前瞻性地研究这些污染物在最近完成的精心设计和严格执行的减肥试验中与人体体重调节有关的作用。这项为期两年的试验的参与者包括811名男性和女性，他们在基线时被随机分为四种低热量饮食。虽然饮食对体重变化有相似的影响，但在短期减肥和随后的体重反弹中观察到大量的个体差异，这不能用依从性或既定的肥胖风险因素来解释。研究人员将分析储存的血浆中PFC的含量，以检查基线PFC水平是否与约700名完成6个月和2年随访的参与者的体重减轻较少和体重恢复较多相关。此外，我们将检查在试验中纵向记录的腰围和全身、腹部和肝脏脂肪含量的关系。研究人员还旨在通过评估血浆PFC浓度与脂肪组织中基因表达谱的关系，以及脂肪因子和甲状腺激素的变化来阐明可能的机制。多学科研究团队由在肥胖研究、环境流行病学、营养学、遗传学和生物统计学方面具有资格和经验的专家组成，从而确保了当前项目的成功实施。这些前瞻性证据将与人类直接相关，可能会导致关于肥胖及其相关疾病结局的新见解和新假设，并有助于制定更全面有效的肥胖预防和治疗策略。

DESCRIPTION (provided by applicant): The proposed study will explore the pathogenesis of human obesity and overweight from a new angle - the possible effects of suspected industrial chemicals in a prospective study. While over-nutrition and sedentary lifestyle are well-established risk factors of obesity, a role of other potential obesity-contributing factors is highy likely and needs to be elucidated. Environmental chemicals known as "obesogens" may upset body weight regulation. Perfluorinated compounds (PFCs) are ubiquitous, persistent chemicals that interfere with energy homeostasis in animal models. However, because of species-specific toxicokinetics, tissue distribution, and mechanisms of action of PFCs, the relevance of animal data to humans is uncertain. Human evidence originated primarily from cross-sectional studies is largely consistent with the hypothesis that PFCs are associated with higher body weight, but lack of prospective data precludes any causal inference. The investigators will, therefore, prospectively examine the roles of these pollutants in relation to human weight regulation in the well-designed and rigorously-implemented POUNDS LOST Trial that was recently completed. The participants of this 2-year trial consist of 811 men and women who were randomized to one of four calorie- reduced diets at baseline. While the diets had similar effects on weight change, substantial between-individual variability was observed in short-term weight-loss and subsequent weight-regain that cannot be explained by compliance or established obesity risk factors. The investigators will analyze banked plasma for PFCs to examine whether baseline PFC levels are associated with less weight-loss and greater weight-regain among ~700 participants who completed 6-month and 2-year follow-up. In addition, we will examine associations with waist circumference and fat content of whole body, abdomen, and liver that were longitudinally recorded in the trial. The investigators also aim to elucidate possible mechanisms by evaluating plasma PFC concentrations in regard to gene expression profiles in adipose tissue, as well as changes of adipokines and thyroid hormones. The multidisciplinary research team is comprised of experts with qualifications and experience in obesity research, environmental epidemiology, nutrition, genetics, and biostatistics, thus ensuring successful implementation of the current project. The prospective evidence will be directly relevant to humans, will likely lead to new insight and hypotheses regarding obesity and related disease outcomes, and will facilitate making more comprehensive and effective strategies for obesity prevention and treatment.