Environmental Chemicals, Adiposity, and Bone Accrual Across Adolescence

青春期的环境化学物质、肥胖和骨质增生

• 批准号: 10328498
• 负责人: Abby Fleisch
• 金额: $ 45.73万
• 依托单位: MAINEHEALTH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10328498
• 关键词: 12 year old; 17 year old; 8 year old; Accounting; Address; Adolescence; Adolescent; Adult; Animal Model; Archives; Area; Behavior; Biological Assay; Biological Markers; Body Composition; Bone Density; Boston; Chemical Exposure; Chemicals; Child; Childhood; Consumption; Data; Development; Diet; Dietary Factors; Dietary History; Disease; Dual-Energy X-Ray Absorptiometry; Endocrine; Endocrinology; Environment; Environmental Exposure; Environmental Impact; Epidemic; Evaluation; Exposure to; Family; Food; Funding; Genetic; Health; Individual; Investigation; Lead; Life; Link; Measurement; Meat; Mediating; Mediator of activation protein; Obesity; Osteoporosis; Osteoporosis prevention; Pathway interactions; Peroxisome Proliferator-Activated Receptors; Physical activity; Plasma; Plasticizers; Policies; Poly-fluoroalkyl substances; Population Study; Positioning Attribute; Predictive Factor; Prevention strategy; Preventive measure; Process; Production; Puberty; Public Health; Research Personnel; Risk; Risk Factors; Role; Scientist; Source; Stains; Suggestion; Testing; Toxic Environmental Substances; United States National Institutes of Health; Urine; Work; adult obesity; animal data; base; bone; bone mass; career; chemical association; cohort; comorbidity; consumer product; cost; critical developmental period; dietary; disorder risk; early adolescence; environmental chemical; epidemiology study; exposed human population; fast food; follow-up; food consumption; insight; novel; obesity in children; obesity prevention; obesity risk; phthalates; preventive intervention; prospective; public health priorities; sociodemographics; substance use; transcription factor; western diet

PROJECT ABSTRACT Obesity and osteoporosis are public health epidemics with costly comorbidities and limited treatment options. Rates of these disorders globally remain unacceptably high, and this is particularly true in the US where 1 in 3 adults are obese and 1 in 25 has osteoporosis. Adiposity and low bone mineral density (BMD) are precursors to these debilitating disorders and track closely from childhood to adulthood. Identifying preventive measures and intervening in early life is critical to curb these epidemics. There are suggestive animal data that chemicals in the environment, per- and polyfluoroalkyl substances (PFASs) and phthalates, may disrupt common mechanistic pathways to concomitantly increase risk of both adiposity and low BMD. Our preliminary data within the prospective Project Viva cohort (~900 children) suggest that children with higher PFAS plasma concentrations in mid-childhood have greater central adiposity and lower BMD by early adolescence. In this proposal, we will expand this prior work. We will extend evaluation through late adolescence, when body composition more strongly predicts adult body composition and related disease risks. We will additionally examine phthalates which act through similar mechanistic pathways as PFASs. We will also employ the novel step of accounting for diet, which has not been comprehensively done in studies of these chemicals, despite the fact that the same Western-style foods that may be a source of chemical exposure also predict risk for adiposity and low BMD. We will accomplish these objectives by first identifying dietary predictors of PFASs and phthlalates in mid-childhood, then examining associations of PFASs and phthalates independent of diet on central adiposity and BMD in late adolescence. Based on our preliminary data suggesting that central adiposity is associated with lower BMD, we will also evaluate the extent to which central adiposity may mediate associations of chemical exposures on BMD. We expect this to be the most comprehensive population-based study to date testing the role of childhood exposures to PFASs and phthalates on development of adiposity and low BMD through adolescence. By examining longitudinal associations across adolescence, we will overcome limitations of many of the existing epidemiologic studies of these chemicals and adiposity, and this will be the first large study to examine the role of these chemicals on BMD in adolescence. Diet, physical activity, and genetics do not explain all of the variability in adiposity and low BMD, and moreover can be difficult to modify. Identifying remediable factors that increase risk of both adiposity and low BMD is a public health priority because this will enable development of preventive strategies to target both conditions. Furthermore, this proposal will advance Dr. Fleisch's career investigating the impact of the toxic environment on endocrine development in childhood with a focus on peripubertal health.

项目摘要 肥胖和骨质疏松症是公共卫生流行病，具有昂贵的合并症和有限的治疗选择。 这些疾病的发生率在全球范围内仍然不可接受，在美国尤其如此，其中3分之一 成年人是肥胖的，而25分之1患有骨质疏松症。肥胖和低骨矿物质密度（BMD）是前体 这些使人衰弱的疾病，从童年到成年。确定预防措施 在早期生活中，对遏制这些流行病至关重要。有暗示性的动物数据化学物质 在环境中，每种和多氟烷基物质（PFASS）和邻苯二甲酸盐可能会破坏常见 机械途径同时增加肥胖和低BMD的风险。我们的初步数据 在潜在项目中，Viva队列（约900名儿童）表明PFAS等血浆的儿童 年龄中期的浓度在青春期初具有更大的中央肥胖和较低的BMD。在这个 提案，我们将扩大这项先前的工作。当身体时，我们将扩展到青春期晚期 组成更强烈地预测成人身体成分和相关疾病风险。我们还将 检查通过与PFASS相似的机械途径起作用的邻苯二甲酸盐。我们还将采用小说 会计饮食的步骤，尽管在这些化学物质的研究中尚未全面做到 可能是化学曝光来源的相同的西式食物也预示了这一事实也可以预测 肥胖和低BMD。我们将通过首先确定PFAS和 phthlalates在中期期间，然后检查PFASS的关联和邻苯二甲酸酯与饮食无关 青春期晚期的中央肥胖和BMD。根据我们的初步数据，表明中心肥胖 与较低的BMD相关，我们还将评估中央肥胖可能介导的程度 BMD上化学暴露的关联。我们希望这将是最全面的基于人群的 迄今为止的研究测试儿童期暴露于PFASS和邻苯二甲酸盐对脂肪发展的作用 通过青春期低的BMD。通过检查整个青春期的纵向关联，我们将 克服许多现有的化学物质和肥胖的现有流行病学研究的局限性，这 将是首次研究这些化学物质在青春期中BMD的作用的大型研究。饮食，身体 活动和遗传学不能解释肥胖和低BMD的所有可变性，而且可以是 难以修改。确定增加肥胖和低BMD风险的可补救因素是公众 健康优先级，因为这将使预防策略能够针对这两种情况。 此外，该提议将推动Fleisch博士的职业生涯调查有毒环境的影响 关于童年的内分泌发展，重点是腹膜健康。