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.

摘要 研究概述：妊娠期母体葡萄糖-胰岛素稳态代表了 最重要的生理过程对孕产妇和儿童健康的结果。虽然 母亲的饮食是这一过程的关键调节器，其影响在不同的国家有很大差异。 这表明其他调节因素可能在起作用。根据研究表明， 饮食和压力在不同的生物和行为水平上相互作用， 压力改变了葡萄糖-胰岛素的稳态，我认为压力可能代表了一种 在怀孕期间具有相当重要的调节作用。然而，现有的怀孕研究 没有考虑到它们的综合影响。K99/R 00项目的主要目标是 为了验证这一假设，母亲产前压力可能会加剧不利的 不健康饮食对妊娠期葡萄糖-胰岛素稳态的影响。我的目标是解决 这个知识差距使用两个互补的方法。目标1：建立 产前应激的独立作用和产前饮食的交互作用 质量和压力，空腹胰岛素抵抗指标（HOMA-IR和Adipo-IR）。目标2： 进行一项随机、对照、交叉研究，以实验性地测试压力暴露是否 增强对标准化膳食的血糖和脂肪酸反应（指示 餐后胰岛素抵抗）。 候选人：我的专业背景是怀孕期间的孕产妇营养， 阐明影响胎儿发育和儿童代谢的产前因素 健康我的研究重点已经扩展到产前压力的作用 并强调生物学。我的职业目标是发展和建立自己作为一个 独立、跨学科的调查员，解决与以下方面有关的关键问题 母亲饮食和压力对产前代谢的影响，以及B）产前生物学如何 可通过母体行为/心理社会状态改变，以改善胎儿编程 结果。我的短期目标是a）了解产前的生化影响， 母亲的饮食压力相互作用，和B）推进这一领域的研究，从观察， 实验研究设计 职业发展：我的培训计划旨在让我获得专业知识， 成功过渡到独立作为一个跨学科的技术技能 调查员它包括定期会议，结构化的课程，重点教程， 在专家指导下的实践培训和研究管理 由Pathik Wadhwa（产前压力，DOHaD）领导的团队，以及共同导师Sonja Entringer（胎儿代谢编程，压力生物学），Janet King（产前营养，代谢）和丹尼尔吉伦 （生物统计学）。 环境：加州大学欧文分校的发展，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，以提供一个智力生产力 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 后代的身体组成、代谢功能和大脑发育。UCI Institute of 临床和转化科学，由NIH临床和转化科学资助 奖励计划，为初级科学家提供研究设计，生物统计学， 社区参与和生物测定平台。