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

研究项目1摘要 鉴于临床和公共卫生负担，消除肥胖症的种族/民族差异是国家的优先事项 以及不良心脏代谢后遗症的成本。肥胖的负担会严重影响 西班牙裔人口，全国患病率超过21%，而非西班牙裔白人为14%。这 肥胖差异在学龄前就已经存在，这表明它可能起源于最早的 人生的各个阶段。越来越多的证据表明，在子宫内或早期的环境暴露- 生命周期有助于肥胖，并可能通过影响食物消耗，基础代谢和 脂肪沉积模式。这些关联背后的生物驱动因素可能是改变了的线粒体 功能-新陈代谢的关键角色之一-也与肥胖和胰岛素有关 阻力鉴于线粒体是胎儿和产后快速生长的主要能量生产者， 环境污染引起的线粒体功能障碍可能会影响与以下相关的早期生命健康结果： 代谢疾病，并可能提供一个合理的机制增加儿童肥胖的风险。在 在加州，暴露于多种环境化学品的负担在 人口，西班牙裔人口承担着有害环境的最大累积负担 暴露。因此，加州的西班牙裔人口不仅肥胖率最高，而且 多重有害环境暴露的不成比例的负担。的累积效应 不成比例的环境暴露可能是肥胖差异的主要驱动因素， 西班牙裔儿童。我们建议调查多种化学环境暴露， 再加上其他已知的肥胖的心理和行为风险因素， 儿童生长轨迹以及婴儿喂养行为和代谢效率。我们将尽 因此，在一个大型的纵向怀孕队列设计中，使用皮质醇评估的尖端技术， 脂肪库定量、最先进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）调查多个预处理和 出生后化学品暴露对出生体重和12个月儿童身高和体重增长轨迹的影响 750名低收入，主要是西班牙裔婴儿; 2）评估这些与环境有关的出生和 a）怀孕期间心理社会压力水平较高的母亲，B） 怀孕前超重/肥胖或怀孕期间体重增加过多，以及c） 暴露于负面的建筑和社会环境; 3）评估是否与环境有关的出生和 婴儿的结果是通过改变能量消耗和线粒体功能介导的;和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名婴儿的子集中使用腹部MRI扫描的<1月龄婴儿的仓库。

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.