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.

项目总结