Prenatal diet-stress interactions and the maternal metabolic response in human pregnancy

摘要 研究综述：妊娠期母体血糖-胰岛素稳态是 对孕产妇和儿童健康结果最重要的生理过程。虽然 母亲的饮食是这一过程的关键调节器，其影响在不同的地方差异很大 个人，这表明其他缓和因素可能正在发挥作用。基于研究表明 饮食和压力在不同的生物和行为水平上相互作用，而生物反应 为了改变血糖-胰岛素的动态平衡，我认为压力很可能代表着 在妊娠中具有相当重要意义的调节剂。然而，现有的怀孕研究 还没有考虑到它们的综合影响。这个K99/R00项目的主要目标是 来检验这样一种假设，即孕期应激可能会加剧不利因素 不良饮食对妊娠期血糖-胰岛素稳态的影响我的目标是解决 这一知识差距使用了两种互补的方法。目标1：建立 产前应激的独立效应和产前饮食的交互作用 质量和压力对空腹胰岛素抵抗指标(HOMA-IR和ADIPO-IR)的影响。目标2：实现 进行一项随机、对照、交叉研究，从实验上测试压力暴露 增强血糖和脂肪酸对标准膳食的反应(表示 孕妇的餐后胰岛素抵抗)。 应聘者：我的背景知识是孕期母体营养和 影响胎儿发育和儿童代谢的产前因素的阐明 健康。我的研究重点现在已经扩展到包括产前应激的作用 以及压力生物学。我的职业目标是发展和确立自己作为一名 独立、跨学科的调查员处理与a)合并的关键问题 母亲饮食和压力对产前代谢的影响，以及b)产前生物学 可以通过母亲的行为/心理社会状态来改变，以改善胎儿编程 结果。我的短期目标是：a)了解营养不良对胎儿的影响 母亲饮食-压力的相互作用，以及b)将这一领域的研究从观察性推进到 实验研究设计。 职业发展计划：我的培训计划旨在让我获得专业和 成功过渡到跨学科独立所需的技术技能 调查员。它包括定期会议、有组织的课程作业、重点教程、 在专家指导下的实训和研究管理 该团队由Pathik Wadhwa(产前应激，DOHaD)领导，以及共同导师Sonja Entringer(胎儿代谢编程，应激生物学)，Janet King(产前营养，新陈代谢)和Daniel Gillen (生物统计学)。 环境：加州大学欧文分校发展、健康和疾病研究计划(DHDRP)提供了无数 资源，包括一个跨学科的团队，以提供智力上的生产力 环境、研究人员、办公室和实验室设施，以及 研究母体-胎盘-胎儿生物学、胎儿发育和 后代的身体成分、代谢功能和大脑发育。UCI学院 由美国国立卫生研究院临床与翻译科学资助的临床与翻译科学 奖励计划，为初级科学家提供研究设计、生物统计学、 社区参与和生物测试平台。

ABSTRACT RESEARCH SUMMARY: Maternal glucose-insulin homeostasis in pregnancy represents one of the most important physiological processes for maternal and child health outcomes. Although maternal diet is a key regulator of this process, its effects vary widely across individuals, suggesting other moderating factors may be at play. Based on studies that demonstrate diet and stress interact at various biological and behavioral levels, and the biological response to stress alters glucose-insulin homeostasis, I submit that stress likely represents a moderator of considerable significance in pregnancy. Yet, existing studies of pregnancy have not considered their combined effects. The primary goal of this K99/R00 project is to test the hypothesis that maternal prenatal stress may exacerbate the unfavorable effects of unhealthy diet on gestational glucose-insulin homeostasis. I aim to address this knowledge gap using two complementary approaches. Aim 1: To establish the independent effect of prenatal stress, and the interaction effect of prenatal diet quality and stress, on indicators of fasting insulin resistance (HOMA-IR and Adipo-IR). Aim 2: To conduct a randomized, controlled, cross-over study to experimentally test whether stress exposure potentiates the glycemic and fatty acid response to a standardized meal (indicative of postprandial insulin resistance) among pregnant women. CANDIDATE: My background expertise is maternal nutrition in pregnancy and the elucidation of prenatal factors that influence fetal development and child metabolic health. My research focus has now expanded to incorporate the role of prenatal stress and stress biology. My career goal is to develop and establish myself as an independent, trans- disciplinary investigator addressing key questions related to a) the combined effects of maternal diet and stress on pre-natal metabolism, and b) how prenatal biology may be altered via maternal behavior/psychosocial state for improved fetal programming outcomes. My short-term goals are a) to understand the prenatal biochemical effects of maternal diet-stress interplay, and b) to advance this field of research from observational to experimental study design. CAREER DEVELOPMENT PLAN: My training plan is designed to allow me to acquire the professional and technical skills necessary for a successful transition to independence as a trans-disciplinary investigator. It includes regular meetings, structured coursework, focused tutorials, practical training and research management under the guidance of an expert mentorship team, led by Pathik Wadhwa (prenatal stress, DOHaD), and co-mentors Sonja Entringer (fetal metabolic programming, stress biology), Janet King (prenatal nutrition, metabolism) and Daniel Gillen (biostatistics). ENVIRONMENT: The UC Irvine Development, Health and Disease Research Program (DHDRP) offers myriad resources, including an inter-disciplinary team to provide an intellectually productive environment, research staff, office, and laboratory facilities, and experiential training in state-of-the-art methods for studies of maternal-placental-fetal bi- ology, fetal development, and offspring body composition, metabolic function and brain development. The UCI Institute of Clinical and Translational Science, funded by the NIH Clinical & Translational Sciences Award program, provides expert support to junior scientists on research design, biostatistics, community engagement and bioassay platforms.