Children Exposure to SVOC Mixtures Indoors and Associations with Obesity

描述（由申请人提供）：婴儿和幼儿95%以上的时间都在室内，由于他们的手到口活动和爬行行为增加，他们接触室内灰尘，长期暴露于半挥发性有机化合物（SVOC）。在室内灰尘中经常检测到的几种SVOC被认为是“化学致肥胖剂”，其被定义为改变脂质稳态和脂肪储存、改变代谢设定点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，围产期暴露于致肥胖剂可能会导致儿童肥胖的几率增加。目前的研究还表明，许多这些化合物的作用机制，包括激活过氧化物酶体增殖物激活核受体（PPARs），导致脂肪形成。我们的初步研究表明，大鼠出生前暴露于环境相关的灰尘混合物在出生时，并在其整个生命中更重。目前测量儿童接触粉尘中化学物质的方法通常依赖于简单和粗略的粉尘摄入率，或 血清或尿液中的测量，后者是昂贵的，并且通常与一种或几种特定的化学物质分离。因此，迫切需要提供更好的估计综合接触SVOC混合物和验证适当的暴露标记。考虑到在一些家庭中发生的慢性和有时高SVOC暴露，我们假设早期生活暴露于室内灰尘中的SVOC混合物会导致儿童肥胖的几率增加，这些影响主要与具有高PPAR的灰尘中的化学物质有关。和脂肪形成活性。为了解决这一假设，我们招募了一个多学科团队，该团队将利用NIH资助的一个正在进行的出生队列的资源并与之合作，该队列研究产前营养，二手烟草烟雾和儿童肥胖的表观遗传学修饰之间的关联。我们将对100名超重/肥胖和100名非肥胖幼儿进行巢式病例对照研究，并使用靶向和非靶向（例如筛查）方法量化其产前和产后对SVOC混合物的暴露。将使用体外试验对室内灰尘样品的脂肪形成和过氧化物酶体增殖体激活受体活性进行表征，这将更深入地了解与实际接触灰尘颗粒相关的影响。肥胖（和研究中提供的其他健康结果），污染物暴露（单个化学品和混合物）和脂肪形成/过氧化物酶体增殖物激活受体？将检查灰尘样本中的放射性。这项工作将提供关于产前和产后接触室内灰尘中的污染物混合物对健康的潜在影响的新数据，并帮助确定缓解因素。

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.