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

产前饮食与压力的相互作用以及人类妊娠期间的母体代谢反应

• 批准号: 10165767
• 负责人: Karen Lindsay
• 金额: $ 24.4万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10165767
• 关键词: Accounting; Acute; Address; Adipose tissue; Affect; Age; Applications Grants; Behavioral; Biochemical; Biological; Biological Assay; Biological Process; Biology; Biometry; Biophysics; Blood specimen; Body Composition; Body mass index; Brain; Child; Clinical; Clinical Sciences; Clinical and Translational Science Awards; Consumption; Cross-Over Studies; Crossover Design; Data; Development; Development Plans; Diet; Dietary Intervention; Dietary intake; Disease; Dose; Ecological momentary assessment; Enrollment; Environment; Ethnic Origin; Exhibits; Exposure to; Fasting; Fatty Acids; Fetal Development; Funding; Future; Gastric Emptying; Gestational Diabetes; Gluconeogenesis; Glucose; Glycemic Index; Goals; Growth; Health; Healthy Eating; Homeostasis; Hour; Human; Hydrocortisone; Individual; Individual Differences; Infant; Institutes; Insulin; Insulin Resistance; Knowledge; Liver; Maternal Behavior; Maternal and Child Health; Measures; Mentors; Mentorship; Metabolic; Metabolic Diseases; Metabolism; Methodology; Methods; Modeling; Moods; Mothers; Nonesterified Fatty Acids; Nutritional Science; Observational Study; Outcome; Pathway interactions; Peripheral; Phase; Physical activity; Physiological Processes; Placebos; Play; Pregnancy; Pregnant Women; Prenatal Nutrition; Process; Protocols documentation; Psychosocial Stress; Race; Randomized; Regulation; Research; Research Design; Research Personnel; Resources; Role; Scientist; Sleep; Smoking; Socioeconomic Status; Standardization; Stress; Structure; Supervision; System; Technical Expertise; Technology; Testing; Third Pregnancy Trimester; Time; Tissues; Training; Training Activity; Translational Research; Trier Social Stress Test; Triglycerides; Unhealthy Diet; United States National Institutes of Health; Variant; Visit; base; biological adaptation to stress; career; career development; cohort; community engagement; data repository; design; dietary; disorder risk; experience; experimental study; fetal; fetal programming; follow-up; gestational weight gain; improved; indexing; infancy; inter-individual variation; laboratory facility; maternal hyperglycemia; maternal stress; meetings; metabolic profile; mother nutrition; non-diabetic; novel; obstetrical complication; offspring; parity; population based; prenatal; prenatal stress; prepregnancy; programs; prospective; psychologic; psychosocial; response; saliva sample; skeletal tissue; smartphone based assessment; sociodemographics; stress reactivity; stress reduction; stressor; western diet

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.

抽象的 研究摘要：妊娠中母体葡​​萄糖胰岛素稳态代表其中之一 孕产妇和儿童健康结果的最重要生理过程。虽然 孕产妇饮食是此过程的关键调节剂，其影响差异很大 个人，表明其他调节因素可能正在发挥作用。基于证明 饮食和压力在各种生物学和行为水平上相互作用，生物学反应 为了改变葡萄糖胰岛素稳态，我认为压力可能代表 主持人在怀孕方面具有相当重要的意义。然而，现有的怀孕研究 尚未考虑它们的综合效果。这个K99/R00项目的主要目标是 为了检验以下假设，即母亲产前压力可能加剧不利 不健康饮食对妊娠葡萄糖胰岛素稳态的影响。我的目标是解决 使用两种互补方法的知识差距。目标1：确定 产前应激的独立效应和产前饮食的相互作用效应 质量和压力，在禁食胰岛素抵抗（HOMA-IR和脂肪IR）的指标上。目标2：到 进行随机，受控的跨界研究，以实验测试应力暴露 增强血糖和脂肪酸对标准餐的反应（表明 餐后胰岛素抵抗）孕妇。 候选人：我的背景专业知识是孕妇营养和 阐明影响胎儿发育和儿童代谢的产前因素 健康。我的研究重点现在已经扩展到结合产前压力的作用 和压力生物学。我的职业目标是发展并确定自己 独立的跨学科研究人员解决了与a）合并的关键问题 产妇饮食和压力对产前代谢的影响，b）产前生物学如何 可以通过孕产妇行为/社会心理状态改变胎儿编程 结果。我的短期目标是a）了解 孕产妇的饮食压力相互作用，b）将研究领域从观察到 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人士和 成功过渡到独立性作为跨学科所必需的技术技能 研究者。它包括定期会议，结构化课程，专注的教程， 在专家指导的指导下实用培训和研究管理 由Pathik Wadhwa（产前压力，DOHAD）和联合委托人Sonja Entringer（胎儿代谢程序，压力生物学），珍妮特·金（Janet King）（产前营养，代谢）和丹尼尔·吉伦（Daniel Gillen）和丹尼尔·吉伦（Daniel Gillen）领导的团队 （生物统计学）。 环境：UC Irvine开发，健康与疾病研究计划（DHDRP）提供了无数 资源，包括一个跨学科团队，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经验培训 孕产妇的养育双重研究，胎儿发育和研究的最新方法 后代身体组成，代谢功能和大脑发育。 UCI研究所 临床和转化科学，由NIH临床和转化科学资助 奖励计划，为研究设计，生物统计学，为初级科学家提供专家支持， 社区参与和生物测定平台。