Inflammation and metabolic abnormalities in pollutant-exposed children

接触污染物的儿童的炎症和代谢异常

• 批准号: 9239171
• 负责人: PHILIPPE ADAM GRANDJEAN
• 金额: $ 17.51万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9239171
• 关键词: 5 year old; 8 year old; 9 year old; Adipose tissue; Adult; Affect; Age; Antibodies; Antibody Response; Benchmarking; Biological Markers; Birth; Blood specimen; Body fat; Body mass index; C-Peptide; Child; Childhood; Clinical; Clinical Data; Comorbidity; Complement; Data; Data Analyses; Databases; Dependence; Depressed mood; Development; Diabetes Mellitus; Dose; Dual-Energy X-Ray Absorptiometry; Dyslipidemias; Environmental Pollutants; Epidemic; Equation; Etiology; Exposure to; Faeroe Islands; Fasting; Fatty acid glycerol esters; General Population; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; Immune System Diseases; Immune System and Related Disorders; Immunologic Markers; Incidence; Infection; Inflammation; Inflammatory; Insulin; Insulin Resistance; Joints; Leptin; Link; Lipids; Measures; Mediating; Metabolic; Metabolic Diseases; Metabolic Marker; Metabolism; Methods; Modeling; Neonatal; Non-Insulin-Dependent Diabetes Mellitus; Nursery Schools; Obesity; Overweight; Pathogenesis; Pilot Projects; Play; Polychlorinated Biphenyls; Population Study; Predisposition; Pregnancy; Prevention; Prospective Studies; Public Health; Regression Analysis; Reporting; Research Design; Risk; Rodent; Role; Sampling; Scanning; Serum; Serum Markers; Skinfold Thickness; Statistical Methods; Time; Tissues; Vaccination; Vaccines; adipokines; adiponectin; age related; clinical phenotype; cofactor; cohort; diabetes risk; early life exposure; environmental chemical; environmental chemical exposure; epidemiology study; exposed human population; fasting glucose; gestational weight gain; immunotoxicity; inflammatory marker; insight; metabolic profile; obesity in children; obesity risk; obesogen; obesogenic; persistent organic pollutants; pollutant; polypeptide C; postnatal; potential biomarker; preadolescence; prenatal; prenatal exposure; prospective; resistin; sex

Project Summary Metabolic diseases, including obesity and type 2 diabetes, are major public health problems of multifactorial etiology, in which early-life exposures to environmental pollutants, such as the perfluoroalkyl substances (PFASs), are suspected to play a role. PFASs have been in use for over 60 years, but omnipresent human exposures were discovered less than 20 years ago, and general population studies of these high-priority pollutants were initiated only recently. We recently discovered that PFAS exposure is associated with depressed antibody response to certain childhood vaccinations. We therefore hypothesize that PFAS-induced inflammation may be involved in the suspected obesogenic effects of PFAS exposure that contribute to the pathogenesis of obesity and metabolic disease. Current evidence, including our own studies, suggests that developmental PFAS exposure may affect metabolic processes in childhood. With the aim to determine the possible link between PFAS exposures, immune dysfunction, and metabolic abnormalities, we will examine at age 8 years an already established birth cohort from the Faroe Islands (N = 490) to explore the associations between age-related PFAS exposure profiles and metabolic abnormalities (using markers of adiposity, dyslipidemia, glycemia and insulin resistance). We will also determine the possible role of metabolic and inflammatory serum markers related to adiposity and insulin action (adipocytokines) and immune dysfunction (vaccine antibody concentrations). Exposure data for PFAS and other environmental pollutants are already available from analyses of maternal pregnancy serum and from clinical examinations at ages 18 months and 5 years. Prospective data and banked serum for potential biomarker analyses are also available from a previous Faroese cohort (N= 656) examined neonatally and at ages 5 and 7.5 years, thus allowing replication studies of new findings. The data analysis will take into account important covariates, such as sex, time of the day for blood sampling, and maternal prepregnancy body mass index and gestational weight gain. Multiple regression analyses will be complemented by structural equation models and other advanced statistical methods, including benchmark dose calculations. The proposed project will provide new insight into the role of high- priority environmental pollutants on metabolic and immune dysfunction, the potential underlying mechanisms and potential new strategies for early prevention of metabolic disease.

项目摘要 代谢疾病，包括肥胖和2型糖尿病，是多因素的主要公共卫生问题 病因，其中早期对环境污染物的暴露，例如全氟烷基物质 （PFAS）被怀疑发挥作用。 PFAS已经使用了60多年，但无所不在的人 不到20年前发现了暴露，并且对这些高优先级的一般人口研究 污染物直到最近才开始。我们最近发现PFAS暴露与 对某些儿童疫苗接种的抑郁抗体反应。因此，我们假设PFAS诱导 炎症可能参与PFA暴露的可疑肥胖作用，这有助于 肥胖和代谢疾病的发病机理。当前的证据，包括我们自己的研究，表明 发育性PFA的暴露可能会影响儿童时期的代谢过程。目的是确定 PFA暴露，免疫功能障碍和代谢异常之间的可能联系，我们将检查 年龄8岁，已经建立了从法罗群岛（N = 490）探索协会的出生队列 在与年龄相关的PFA暴露概况和代谢异常之间（使用肥胖标记， 血脂异常，糖血症和胰岛素抵抗）。我们还将确定代谢和 与肥胖和胰岛素作用（脂肪细胞因子）和免疫功能障碍有关的炎症血清标记物 （疫苗抗体浓度）。 PFA和其他环境污染物的暴露数据已经是 可从孕产妇妊娠血清的分析以及18个月的临床检查可获得5个月 年。前面的生物标志物分析的预期数据和库存血清也可以从以前的 Faroese队列（n = 656）在5岁和7.5岁时对新生儿进行了检查，从而允许复制研究 新发现。数据分析将考虑重要的协变量，例如性别，一天中的时间 血液采样，母体孕前体重指数和妊娠体重增加。多重回归 分析将由结构方程模型和其他高级统计方法互补， 包括基准剂量计算。拟议的项目将提供有关高级作用的新见解 优先环境污染物对代谢和免疫功能障碍，潜在的潜在机制 以及早期预防代谢疾病的潜在新策略。