Children Exposure to SVOC Mixtures Indoors and Associations with Obesity

描述（由申请人提供）：婴幼儿在室内的时间超过95%，由于他们的手到嘴活动和爬行行为增加，他们长期暴露于与室内灰尘接触的半挥发性有机化合物（SVOCs）。室内粉尘中常见的几种SVOCs被认为是“化学致肥源”，它被定义为改变脂质稳态和脂肪储存、改变代谢设定值或破坏能量平衡的化学物质，导致脂肪积累和肥胖。最近的几项研究表明，围产期接触致肥物可能会导致儿童肥胖的几率增加。目前的研究还表明，许多这些化合物通过激活过氧化物酶体增殖物激活的核受体（PPARs）的机制起作用，导致脂肪形成。我们的初步研究表明，大鼠在出生时暴露于与环境相关的粉尘混合物中，并且在其一生中都更重。目前测量儿童接触粉尘中存在的化学物质的方法通常依赖于简单和粗略的粉尘摄入率，或者

DESCRIPTION (provided by applicant): 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 PPAR? 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/PPAR? 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.