Biological Embedding of Childhood Obesity: Stress Responsive Systems and Sleep

项目摘要/摘要 大约五分之一的美国儿童患有肥胖症。儿童肥胖对成年人有重大的长期影响 健康。尽管联邦政府采取了针对体力活动和营养的举措，但儿童肥胖率并没有 在过去的二十年里，这一数字显著下降。这需要更多地关注实例化风险的因素。 为以后的肥胖做准备。很少有关于压力生物学和儿童肥胖症的研究采用纵向设计。 压力测量，或跨多个生物系统集成，尽管越来越多的人认识到 它们复杂的相互作用。目前的提案试图通过整合几个 将儿童早期的生物和发育系统转化为日后超重的预测模型/ 肥胖。感兴趣的生物系统包括交感肾上腺-延髓(SAM)系统，该系统迅速 触发对应激源的生理和行为反应，下丘脑-垂体-肾上腺(HPA)轴，a 荷尔蒙反应系统对长期应激源做出反应。本研究利用收集到的数据(RC1DK086376 PI：Lumeng/Miller)检查：(1)SAM系统和HPA轴之间的通路在 幼儿标准化应激任务与儿童期中期体重指数(BMI)的关系 从学龄前到儿童中期，行为睡眠质量和BMI之间的纵向关联 (3)行为睡眠质量在SAM系统与HPA纵向关系中的调节作用 学龄前儿童轴心应激反应与儿童中期体重指数孩子们在整个过程中提供了唾液样本 标准化应激任务，皮质醇(HPA轴的主要输出)和α-淀粉酶(指示 SAM系统活性)。结果将阐明超重风险的早期生物学嵌入/ 并可告知同时采取有效干预措施的类型和时机。一项广泛的培训计划包括 与当前的研究一起设计，以使申请者具备独立学习所需的技能 临床科学家的研究生涯。奖学金培训的目标是：(1)提炼独特的研究兴趣 和临床科学家职业生涯的定位，从而导致有影响力的研究计划，(2)学习 独立运营实验室，(3)掌握适用于纵向、多维数据的统计建模技能 代表几个生物系统，(4)建立富有成效的双向社区伙伴关系和技能 在传播研究方面，以及(5)发展赠款撰写技能。申请人已经召集了一个专门的，相互之间的 拥有睡眠、压力生物学、肥胖途径、家庭等相关专业知识的科学家组成的学科团队 背景因素，以及社区-学术伙伴关系。培训活动将主要在以下部分进行- 丹佛大学心理学系，教授跨学科的发展心理学-- 使用各种方法(例如，功能磁共振成像、炎症标记物)进行生物学研究。这笔培训补助金将 推动一个独立的研究计划，调查睡眠、压力和儿童健康的关键交叉点。

PROJECT SUMMARY/ABSTRACT About a fifth of U.S. children are obese. Pediatric obesity has significant long-term ramifications for adult health. Despite federal initiatives targeting physical activity and nutrition, rates of pediatric obesity have not significantly decreased in the last two decades. This warrants increased attention to factors instantiating risk for later obesity. Few studies examining stress biology and child obesity utilize longitudinal designs, objective measures of stress, or integrate across multiple biological systems despite increasing acknowledgement of their complicated interplay. The current proposal seeks to address gaps in the literature by integrating several biological and developmental systems during early childhood into a predictive model for later overweight/ obesity. Biological systems of interest include the Sympathetic Adrenal-Medullary (SAM) System, which quickly triggers physiologic and behavioral reactions to stressors, and Hypothalamic-Pituitary-Adrenal (HPA) Axis, a hormonal response system reacting to longer-term stressors. This study utilizes collected data (RC1DK086376 PI: Lumeng/Miller) to examine: (1) pathways between SAM system and HPA Axis functioning during a standardized stress task in toddlers and body-mass index (BMI) in middle childhood, (2) bi-directional longitudinal associations between behavioral sleep quality and BMI across preschool to middle childhood, and (3) the moderating role of behavioral sleep quality in longitudinal relationships between SAM system and HPA axis stress reactivity in preschool and BMI in middle childhood. Children provided saliva samples throughout a standardized stress task, from which cortisol (primary output of the HPA axis) and alpha amylase (indicating SAM system activity) were assayed. Results will elucidate early biological embedding of risk for overweight/ obesity and can inform concurrent type and timing of effective interventions. An extensive training plan has been designed alongside the current study to equip the applicant with skills needed for an independent research career as a clinical scientist. Fellowship training goals are to: (1) Refine distinct research interests and position for a clinical scientist career leading to an impactful research program, (2) Learn skills needed to independently run a lab, (3) Hone skills in statistical modeling suited for longitudinal, multi-dimensional data representing several biological systems, (4) Build productive, bi-directional community partnerships and skills in disseminating research, and (5) Develop grant-writing skills. The applicant has assembled a dedicated, inter- disciplinary team of scientists with relevant expertise in sleep, stress biology, obesogenic pathways, family contextual factors, and community-academic partnerships. Training activities will primarily occur in the Depart- ment of Psychology, University of Denver, where faculty conduct interdisciplinary, developmental psycho- biology research using a variety of methodologies (e.g., fMRI, inflammatory markers). This training grant will catalyze an independent research program investigating critical intersections of sleep, stress, and child health.