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
基本信息
- 批准号:10444523
- 负责人:
- 金额:$ 53.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:12 year oldAdipocytesAdolescenceAdultAffectAgeAndrogen ReceptorBiologicalBiological MarkersBirthBlood PressureBody BurdenBody fatBody mass indexC-reactive proteinCanadaChemicalsChildCholesterolChronicComplexDataDevelopmentDietDyslipidemiasEndocrine DisruptorsEnvironmentEnvironmental ExposureEnvironmental PolicyEstersEstrogen ReceptorsExposure toFamilyFastingFatty acid glycerol estersFlame RetardantsGeneral PopulationGeneticGlucoseGlycoproteinsGonadal Steroid HormonesGrowthHealthHealth ResourcesHeart DiseasesHip region structureHomeostasisHormonesHumanHypertensionIndividualInfantInflammationInsulinInsulin ResistanceInterleukin-6JointsLeptinLifeLipidsLipolysisLipoproteinsLongitudinal StudiesMeasurementMeasuresMetabolicMetabolic syndromeMetabolismModelingModernizationMolecular WeightNon-Insulin-Dependent Diabetes MellitusObesityOrganophosphatesOutcomeOutcome MeasureOverweightOxidative StressPPAR alphaPathogenesisPathway interactionsPerinatalPeroxisome Proliferator-Activated ReceptorsPhasePhysical activityPlasticizersPlayPolicy MakingPredispositionPregnancyPregnant WomenPrevalenceProspective StudiesPublic HealthReportingResearchResearch DesignRisk FactorsRodentRoleSerumStatistical MethodsTNF geneThermogenesisThyroid HormonesTimeTissuesToxicologyTriglyceridesUnited Statesadiponectincardiometabolismcohortearly adolescenceearly life exposureenvironmental chemicalepidemiology studyfasting glucosehigh riskimpaired glucose toleranceindexinginorganic phosphatelipid biosynthesislipid metabolismmetabolic profilenovelnovel markerobesity developmentobesity in childrenobesity riskobesogenobesogenicparticlepollutantpolybrominated diphenyl etherpostnatalpostnatal periodprenatalprenatal exposureprospectivetraittranscription factortris(2-carboxyethyl)phosphineurinarywaist circumference
项目摘要
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
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Ann Vuong', 18)}}的其他基金
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:
10707932 - 财政年份:2022
- 资助金额:
$ 53.61万 - 项目类别:
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