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
• 负责人: Ann Vuong
• 金额: $ 49.52万
• 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/10707932
• 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 Induction; 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; 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 Induction; 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.

项目摘要 近几十年来，儿童肥胖症患病率的急剧增加使肥胖成为其中之一 现代世界最大的公共卫生挑战。据估计，到2030年，我们中的33％和50％ 6-11岁和12-19岁的儿童将超重或肥胖。环境暴露 子宫及在产后易感性增强期间可能会增加肥胖的风险和不利 撞击心脏代谢健康。有机磷酸酯（OPES）是添加剂阻燃剂和增塑剂 多溴二苯基醚（PBDES）逐步淘汰后，全球范围内广泛使用。这 无处不在使用OPES，几乎所有孕妇都有OPE暴露和儿童 与成人相比，身体负担更高。 Opes干扰了公认的生物学途径 肥胖和心脏代谢健康的发展，包括：1）甲状腺激素； 2）性 类固醇激素； 3）过氧化物酶体增殖物激活的受体以及诱导4） 炎。毒理学研究表明，OPES增加了脂质的积累，中断的代谢功能和 损害葡萄糖耐受性，支持它们作为潜在的肥胖和代谢破坏化学物质的作用。 流行病学研究报告说，超重和肥胖以及腰部更高的几率增加了 周长，体重指数（BMI），总胆固醇和甘油三酸酯。但是，没有纵向研究 人类已经检查了早期生活中反复的OPE措施，以及他们与肥胖和 青春期心脏代谢健康，这是一个重要的数据差​​距。该建议的申请将大写 关于健康结果和环境措施（家庭）研究的资源 首先要检查早期生活是否与肥胖和心脏代谢健康指标有关 青春期，包括BMI和腰围Z得分，脂肪量指数，体内脂肪％，血压，血压， 使用前瞻性研究设计，禁食葡萄糖，血清脂质，脂联素和瘦素。我们还将 测量新型心脏代谢中间体，包括高分子量脂联素，糖蛋白 乙酰基（Glyca），虹膜蛋白，Vaspin和脂蛋白颗粒以及炎症的生物标志物。我们将使用 分位数G-Compunt（Q-GCOMP）和贝叶斯内核机回归（BKMR）检查复杂 OPE混合物确定OPES对肥胖和心脏代谢轮廓的个体和关节影响 青春期。我们将使用来自孕产妇的环境化学研究的数据（MIREC） 研究是泛加拿大队列的研究，以验证家庭研究中的发现。我们将产生新颖的发现 早期生命的opes是否是肥胖的和新陈代谢的化学物质，并确定 易感性的潜在窗户。鉴于Opes的普遍性和肥胖和类型2的全球负担 糖尿病，这些发现对于降低环境政策制定和暴露量将非常有价值。