Early life organophosphate ester (OPE) exposures and adiposity and cardiometabolic health during adolescence

生命早期有机磷酸酯 (OPE) 暴露与青春期肥胖和心脏代谢健康

• 批准号: 10444523
• 负责人: Ann Vuong
• 金额: $ 53.61万
• 依托单位: UNIVERSITY OF NEVADA LAS VEGAS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10444523
• 关键词: 12 year old; Adipocytes; Adolescence; Adult; Affect; Age; Androgen Receptor; Biological; Biological Markers; Birth; Blood Pressure; Body Burden; Body fat; Body mass index; C-reactive protein; Canada; Chemicals; Child; Cholesterol; Chronic; Complex; Data; Development; Diet; Dyslipidemias; Endocrine Disruptors; Environment; Environmental Exposure; Environmental Policy; Esters; Estrogen Receptors; Exposure to; Family; Fasting; Fatty acid glycerol esters; Flame Retardants; General Population; Genetic; Glucose; Glycoproteins; Gonadal Steroid Hormones; Growth; Health; Health Resources; Heart Diseases; Hip region structure; Homeostasis; Hormones; Human; Hypertension; Individual; Infant; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Joints; Leptin; Life; Lipids; Lipolysis; Lipoproteins; Longitudinal Studies; Measurement; Measures; Metabolic; Metabolic syndrome; Metabolism; Modeling; Modernization; Molecular Weight; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organophosphates; Outcome; Outcome Measure; Overweight; Oxidative Stress; PPAR alpha; Pathogenesis; Pathway interactions; Perinatal; Peroxisome Proliferator-Activated Receptors; Phase; Physical activity; Plasticizers; Play; Policy Making; Predisposition; Pregnancy; Pregnant Women; Prevalence; Prospective Studies; Public Health; Reporting; Research; Research Design; Risk Factors; Rodent; Role; Serum; Statistical Methods; TNF gene; Thermogenesis; Thyroid Hormones; Time; Tissues; Toxicology; Triglycerides; United States; adiponectin; cardiometabolism; cohort; early adolescence; early life exposure; environmental chemical; epidemiology study; fasting glucose; high risk; impaired glucose tolerance; indexing; inorganic phosphate; lipid biosynthesis; lipid metabolism; metabolic profile; novel; novel marker; obesity development; obesity in children; obesity risk; obesogen; obesogenic; particle; pollutant; polybrominated diphenyl ether; postnatal; postnatal period; prenatal; prenatal exposure; prospective; trait; transcription factor; tris(2-carboxyethyl)phosphine; urinary; waist circumference

PROJECT SUMMARY The dramatic increase in the prevalence of childhood obesity in recent decades has made obesity one of the greatest public health challenges of the modern world. It is estimated that by 2030, 33% and 50% of US children ages 6-11 and 12-19 years, respectively, will be overweight or obese. Environmental exposures in utero and during postnatal periods of heightened susceptibility may increase risk of obesity and adversely impact cardiometabolic health. Organophosphate esters (OPEs) are additive flame retardants and plasticizers that are extensively used worldwide after the phase-out of polybrominated diphenyl ethers (PBDEs). The ubiquitous use of OPEs has resulted in almost all pregnant women having OPE exposures and children having a higher body burden compared to adults. OPEs interfere with well-recognized biological pathways contributing to the development of obesity and cardiometabolic health, including disruption of: 1) thyroid hormones; 2) sex steroid hormones; and 3) peroxisome proliferator-activated receptors as well as inducing 4) chronic low-grade inflammation. Toxicological studies indicate OPEs increase lipid accumulation, disrupt metabolic function, and impair glucose tolerance, supporting their role as potential obesogenic and metabolism-disrupting chemicals. Epidemiological studies report increased odds of being overweight and obese as well as higher waist circumference, body mass index (BMI), total cholesterol, and triglycerides. However, no longitudinal study in humans has examined repeated OPE measures in early life and their association with adiposity and cardiometabolic health in adolescence, which is a significant data gap. This proposed application will capitalize on resources of the Health Outcomes and Measures of the Environment (HOME) Study to be among the very first to examine whether early life OPEs are associated with adiposity and cardiometabolic health measures in adolescence, including BMI and waist circumference z-scores, fat-mass index, body fat %, blood pressure, fasting glucose, serum lipids, adiponectin, and leptin, using a prospective study design. We will additionally measure novel cardiometabolic intermediates, including high molecular weight adiponectin, glycoprotein acetyls (GlycA), irisin, vaspin, and lipoprotein particles, as well as biomarkers of inflammation. We will use Quantile g-computation (Q-gcomp) and Bayesian Kernel Machine Regression (BKMR) to examine complex OPE mixtures to determine the individual and joint effects of OPEs on adiposity and cardiometabolic profiles in adolescence. We will use data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort, to validate findings from the HOME Study. We will generate novel findings on whether early life OPEs are obesogenic and metabolism-disrupting chemicals during adolescence and identify potential windows of susceptibility. Given the ubiquity of OPEs and the global burden of obesity and type 2 diabetes, the findings will be highly valuable for environmental policy making and exposure reduction.

项目总结