Project 1: Effects of Air Pollution on the Development of Obesity in Children

项目1：空气污染对儿童肥胖发展的影响

• 批准号: 8875809
• 负责人: FRANK D. GILLILAND
• 金额: $ 0.41万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-20 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8875809
• 关键词: 18 year old; Accounting; Adipose tissue; Adverse effects; Affect; Age; Air Pollution; Animal Model; Beta Cell; Birth Certificates; Blood Pressure; Body fat; Body mass index; Breathing; CCL2 gene; California; Carbon; Cardiovascular Diseases; Cell physiology; Child; Child health care; Childhood; Chronic; Cohort Studies; Communities; Data; Deposition; Development; Drug or chemical Tissue Distribution; Dyslipidemias; Elderly; Environmental Exposure; Environmental Health; Exposure to; Fatty acid glycerol esters; Functional disorder; Gender; Glucose; Growth; Health; Health Status; Hepatic; Imaging Techniques; Inflammation; Inflammatory Response; Insulin Resistance; Interleukin-6; Leptin; Life; Link; Lipids; Liver diseases; Magnetic Resonance Imaging; Measures; Mediating; Mediation; Mediator of activation protein; Metabolic; Metabolic Diseases; Metabolic syndrome; Metal exposure; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Overweight; Oxidative Stress; Pancreas; Participant; Particle Size; Pattern; Phenotype; Physical activity; Play; Pregnancy; Prevalence; Prevention; Preventive Intervention; Public Health; Reactive Oxygen Species; Relative (related person); Risk; Role; Sampling; Structure of beta Cell of islet; TNF gene; Time; Tobacco Smoke Pollution; Transition Elements; Visceral; adipokines; adiponectin; base; cohort; critical developmental period; critical period; density; early life exposure; in utero; inflammatory marker; insulin sensitivity; interest; intravenous glucose tolerance test; knowledge base; non-alcoholic fatty liver; novel; obesity in children; obesity risk; physical conditioning; prenatal; research study; resistin; spatiotemporal; trafficking

Obesity and its metabolic consequences have become critical public health issues. A better understanding of the causes of childhood obesity is needed to develop the effective preventive intervention. Recent studies indicate that early-life exposures to near roadway traffic-related air pollution (NRAP) increase childhood obesity and have the potential to contribute to fat redistribution, systemic inflammation, and metabolic changes associated with increased risk for type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Although childhood NRAP exposure is associated with increased risk for obesity, there is little data on the effects in children of exposures during critical period of development on the distribution of adipose tissue or the metabolic consequences of exposure. This application proposes to fill critical gaps in thte scientific (knowledge base by investigating the effects of elevated NRAP exposures during the in utero and childhood periods on clinically important obesity phenotypes, obesity-related inflammation and adipokines, insulin sensitivity, beta-cell function and components ofthe metabolic syndrome (MetS). We have identified elemental carbon (EC) mass in the particle size fraction less than 2.5 microns (EC2.5) and pro-oxidant PM2.5 transition metals (Fe, Cu,) as components of NRAP that have the largest potential contribution to the adverse health effects based on evidence that these traffic-related PM components produce systemic oxidative stress and inflammation. We hypothesize that prenatal, early and later childhood exposures have clinically important effects on the trajectories toward obesity (BMI, and percent body fat) and increase visceral adipose tissue (VAT) deposition resulting in systemic inflammation and metabolic complications including abnormal pancreatic beta cell function and changes in components of MetS including insulin resistance, dyslipidemia and elevated blood pressure. We will use the extensive data on exposures and health outcomes in the Southern California Children's Health Study (CHS) to assess specific hypotheses.

肥胖及其代谢后果已成为关键的公共卫生问题。更好地了解 需要对儿童肥胖的病因进行研究，制定有效的预防干预措施。最近的研究 表明早期暴露于近道路交通相关空气污染（NRAP）会增加儿童肥胖 并有可能导致脂肪再分布、全身炎症和代谢变化 与2型糖尿病、非酒精性脂肪性肝病（NAFLD）的风险增加相关， 心血管疾病（CVD）。虽然儿童期接触NRAP与以下风险增加有关： 关于儿童在发育的关键时期暴露对肥胖的影响， 脂肪组织的分布或暴露的代谢后果。本申请旨在填补 通过调查国家行动方案暴露量增加的影响， 在子宫内和儿童期对临床上重要的肥胖表型，肥胖相关 炎症和脂肪因子，胰岛素敏感性，β细胞功能和代谢的成分 综合征（MetS）。我们已经确定了小于2.5的颗粒尺寸部分中的元素碳（EC）质量 微米（EC2.5）和助氧化剂PM2.5过渡金属（Fe、Cu）作为NRAP的成分，具有最大的 潜在的贡献，对健康的不利影响的基础上，这些交通相关的PM成分的证据， 产生全身性氧化应激和炎症。我们假设产前，早期和晚期的儿童 暴露对肥胖的轨迹（BMI和体脂百分比）具有临床重要影响， 内脏脂肪组织（VAT）沉积增加，导致全身炎症和代谢 并发症，包括胰腺β细胞功能异常和MetS组分的变化，包括 胰岛素抵抗、血脂异常和血压升高。我们将使用大量的暴露数据， 健康结果在南加州儿童健康研究（CHS），以评估特定的假设。