Infants and young children spend more than 95% of their time indoors where they receive chronic exposures to semi-volatile organic compounds (SVOCs) from contact with indoor dust due to their increased hand to mouth activity and crawling behavior. Several SVOCs commonly detected in indoor dust are considered "chemical obesogens", which are defined as chemicals that alter lipid homeostasis and fat storage, alter metabolic set points, or disrupt energy balance, resulting in fat accumulation and obesity. Several recent studies have suggested that perinatal exposure to obesogens may result in increased odds of obesity in children. Current research also suggests that many of these chemicals compounds act via a mechanism that includes activation of peroxisome proliferator-activated nuclear receptors (PPARs), leading to adipogenesis. Our preliminary studies demonstrate that rats prenatally exposed to an environmentally relevant dust mixture were heavier at birth, and throughout their life. Current approaches to measuring children's exposure to chemicals present in dust have typically relied on simplistic and crude dust ingestion rates, or measurements in serum or urine, the latter being expensive and typically isolated to one or few specific chemicals. Therefore, there is a critical need to provide better estimates of integrated exposure to SVOC mixtures and validate appropriate exposure markers. Given the chronic and sometimes high SVOC exposure that occurs in some homes, we hypothesize that early life exposure to mixtures of SVOCs in indoor dust leads to increased odds of obesity in children, and that these effects are associated primarily with chemicals in dust having high PPARγ and adipogenic activity. To address this hypothesis we have recruited a multi-disciplinary team that will leverage the resources of, and collaborate with, an ongoing NIH funded birth cohort examining associations between prenatal nutrition, secondhand tobacco smoke, and epigenetics modifications on obesity in children. We will conduct a nested case control study with 100 overweight/obese and 100 non-obese toddlers and quantify their prenatal and postnatal exposure to mixtures of SVOCs using targeted and non-targeted (e.g. screening) approaches. House dust samples will be characterized for both adipogenic and PPAR activity using in vitro assays, which will provide greater insight into effects related to actual exposure t dust particles. Associations between obesity (and other health outcomes available in the study), contaminant exposure (individual chemicals and mixtures) and adipogenic/PPARγ activity in dust samples will be examined. This work will contribute new data regarding the potential health impacts from pre- and postnatal exposure to contaminant mixtures present in house dust, and help identify mitigating factors. ExpandCollapse Abstract