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.
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