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

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 需要对儿童肥胖的病因进行有效的预防干预。最新研究 表明早年暴露在与道路交通相关的空气污染(NRAP)中会增加儿童肥胖 并有可能促进脂肪重新分配、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)风险增加相关，以及 心血管疾病(CVD)。尽管儿童时期接触NRAP与罹患 对于肥胖来说，在发育的关键时期暴露对儿童的影响的数据很少。 脂肪组织的分布或暴露的代谢后果。此应用程序建议填写 通过调查增加的NRAP暴露的影响，在科学(知识库)中的关键差距 在宫内和儿童期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细胞功能和代谢成分 综合征(METS)。我们已经在小于2.5的粒度分数中确定了元素碳(EC)质量 微米(EC2.5)和助氧化剂PM2.5过渡金属(Fe，Cu，)作为NRAP的最大成分 根据这些与交通相关的PM成分的证据，可能会对健康造成不利影响 产生全身性氧化应激和炎症。我们假设，出生前、早期和后期的儿童 暴露在临床上对肥胖的轨迹(BMI和体脂百分比)和 增加内脏脂肪组织(VAT)沉积，导致全身炎症和代谢 并发症包括胰岛β细胞功能异常和蛋氨酸的成分变化，包括 胰岛素抵抗、血脂异常和血压升高。我们将使用大量的曝光数据和 南加州儿童健康研究(CHS)中的健康结果，以评估特定的假设。

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.