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

基本信息

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
项目类别：
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

项目摘要

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。更好地理解需要儿童肥胖的原因来开发有效的预防性干预。最近的研究表明早期寿命暴露于近路交通相关的空气污染（NRAP）增加儿童肥胖症并有可能导致脂肪再分配，全身性炎症和代谢变化与增加2型糖尿病的风险增加有关，非酒精性脂肪肝病（NAFLD）和心血管疾病（CVD）。尽管儿童时期的NRAP暴露与增加的风险有关肥胖，在关键发展期间对儿童的影响的影响很少脂肪组织的分布或暴露的代谢后果。本申请建议填写科学的临界差距（通过研究升高NRAP暴露的影响，知识基础在临床上重要的肥胖表型上的子宫和童年期间，与肥胖有关炎症和脂肪因子，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的粒径分数中的元素碳（EC）质量微米（EC2.5）和促氧化剂PM2.5过渡金属（Fe，Cu，）作为NRAP的组成部分，该组件具有最大的基于这些与交通相关的PM组件的证据，对不良健康影响的潜在贡献产生全身氧化应激和炎症。我们假设那个产前，早期和较晚的童年暴露对肥胖（BMI和体内脂肪百分比）和增加内脏脂肪组织（VAT）沉积，导致全身炎症和代谢并发症，包括异常胰腺β细胞功能以及Mets组成部分的变化，包括胰岛素抵抗，血脂异常和血压升高。我们将使用有关暴露的广泛数据和南加州儿童健康研究（CHS）的健康成果，以评估特定的假设。