Project 1: Cumulative prenatal and infant environmental exposures and early childhood obesity risk

研究项目1摘要 鉴于肥胖的临床和公共卫生负担，消除肥胖的种族/民族差异是国家的优先事项 以及不利的心脏代谢后遗症的费用。肥胖的负担不成比例地影响着 西班牙裔人口，全国患病率超过21%，而非西班牙裔白人的患病率为14%。这 肥胖差距在学龄前就已经存在，这表明肥胖症最早可能起源于 生命的各个阶段。越来越多的证据表明，在宫内或早期接触环境- 生命周期导致肥胖，并可能通过影响食物消耗、基础代谢和 脂肪沉积的模式。这些关联背后的生物驱动因素可能是线粒体的改变 功能--新陈代谢的关键因素之一--也与肥胖和胰岛素有关 抵抗。鉴于线粒体是胎儿和出生后快速生长的主要能量来源， 环境暴露诱导的线粒体功能障碍可能影响与以下相关的早期生命健康结局 代谢性疾病，并可能为儿童肥胖风险增加提供一个看似合理的机制。在……里面 在加利福尼亚州，接触多种环境化学品的负担并不均匀地分布在 人口，其中西班牙裔人口承担着最大的累积有害环境负担 曝光。因此，加州的西班牙裔人口不仅是肥胖率最高的人群之一，而且 多种有害环境暴露的不成比例的负担。这些措施的累积效应 不成比例的环境暴露可能是导致肥胖差异的主要驱动因素 在西班牙裔儿童中。我们建议调查多重化学环境暴露是如何， 再加上其他已知的肥胖的心理社会和行为风险因素，总体上影响早期 儿童的生长轨迹以及婴儿的喂养行为和代谢效率。我们会做的 因此，在一项大型纵向妊娠队列设计中，使用皮质醇评估和前沿技术 脂肪库量化、最新的统计方法和评估线粒体的新方法 功能。项目1将解决以下目标：1)调查多个事前和事后的累积影响 出生后化学物质暴露对出生体重和12个月儿童身高和体重增长轨迹的影响 750名低收入婴儿，主要是西班牙裔婴儿；2)评估这些与环境有关的分娩和 母亲在怀孕期间心理社会压力水平较高的婴儿的婴儿结局较大，b) 谁在怀孕前超重/肥胖或在怀孕期间超重，以及c)有更多 暴露在负面的建筑和社会环境中；3)评估与环境有关的分娩和 婴儿的结局通过改变能量消耗和线粒体功能来调节；以及4) 检查产前环境暴露和皮质醇水平对腹部脂肪的累积影响 在40名婴儿的子组中，使用腹部MRI扫描1个月大的婴儿的仓库。

RESEARCH PROJECT 1 ABSTRACT Eliminating racial/ethnic disparities in obesity is a national priority given the clinical and public health burden and costs of the adverse cardio-metabolic sequelae. The burden of obesity disproportionally affects the Hispanic population, with prevalence in excess of 21% nationally compared to 14% non-Hispanic whites. This obesity disparity is already present by preschool age, suggesting that it may have its origins in the earliest stages of life. A growing body of evidence suggests that environmental exposures during the in utero or early- life periods contribute to obesity and may be doing so by affecting food consumption, basal metabolism and patterns of adipose deposition. The biological driver behind these associations may be altered mitochondrial function – one of the key players in metabolism – which has also been associated with obesity and insulin resistance. Given that mitochondria are the primary energy producers for rapid fetal and postnatal growth, environmental exposure-induced mitochondrial dysfunction may affect early life health outcomes related to metabolic disease and may provide a plausible mechanism underlying increased childhood obesity risks. In California, the burden of exposures to multiple environmental chemicals is not evenly distributed in the population, with the Hispanic population carrying the greatest cumulative burden of harmful environmental exposures. Thus, the Hispanic population in California not only has one of the highest rates of obesity but also a disproportionate burden of multiple harmful environmental exposures. The cumulative effects of the disproportionate environmental exposures may be a primary driving factor underlying the disparities in obesity among Hispanic children. We propose to investigate how multiple chemical environmental exposures, coupled with other known psychosocial and behavioral risk factors for obesity, affect overall early childhood growth trajectories as well as infant feeding behaviors and metabolic efficiency. We will do so in a large longitudinal pregnancy cohort design, using cutting-edge technologies of cortisol assessment and fat depot quantification, state-of-the-art statistical methods, and novel methods for evaluating mitochondrial function. Project 1 will address the following aims: 1) To investigate the cumulative effects of multiple pre- and postnatal chemical exposures on birth weight and 12 month childhood height and weight growth trajectories for 750 low-income, primarily Hispanic infants; 2) to evaluate whether these environmentally-related birth and infant outcomes are larger in infants of mothers a) with high levels of psychosocial stress during pregnancy, b) who are overweight/obese before pregnancy or gain excess weight during pregnancy, and c) who have greater exposures to negative built and social environments; 3) to evaluate whether environmentally-related birth and infant outcomes are mediated through altered energy consumption and mitochondrial function; and 4) to examine the cumulative effects of prenatal environmental exposures and cortisol levels on abdominal fat depots of infants at <1 month of age using abdominal MRI scans in a subset of 40 infants.