Fetal Programming of Growth and Obesity: A Metabolomics Approach

胎儿生长和肥胖的编程：代谢组学方法

• 批准号: 9908073
• 负责人: Yeyi Zhu
• 金额: $ 16.25万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908073
• 关键词: Adult; Affect; Age; Area; Bioinformatics; Biological; Biological Markers; Biometry; Birth; Body mass index; Branched-Chain Amino Acids; California; Caucasians; Child; Clinical; Complement; Data; Data Collection; Diet; Dietary Factors; Disease; Elderly; Electronic Health Record; Environment; Epidemiology; Etiology; Fasting; Fatty Acids; Fetal Growth; First Pregnancy Trimester; Foundations; Functional disorder; Gestational Age; Glucose; Goals; Growth; Human; Impairment; Individual; Infant; Inositol; Insulin; Integrated Health Care Systems; Investigation; K-Series Research Career Programs; Knowledge; Length; Life; Life Style; Measurement; Measures; Mentorship; Metabolic; Metabolic Pathway; Metabolism; Nonesterified Fatty Acids; Obesity; Obesity Epidemic; Overnutrition; Overweight; Pathway interactions; Phenotype; Physical activity; Predisposition; Pregnancy; Prevention; Preventive; Prospective cohort; Psychosocial Assessment and Care; Research; Research Personnel; Resources; Risk; Sampling; Second Pregnancy Trimester; Serum; Shapes; Small for Gestational Age Infant; Solid; Source; Surveys; Technology; Training; Training Programs; Validation; Weight; Whole Organism; Work; acylcarnitine; aged; base; cardiometabolic risk; cardiometabolism; career; comorbidity; experience; fetal; fetal programming; follow-up; gut microbiota; hands-on learning; high risk; human data; in utero; indexing; individualized prevention; infancy; metabolomics; mitochondrial dysfunction; multidisciplinary; novel; nutrition; obesity in children; obesity prevention; obesity risk; offspring; personalized care; prenatal exposure; programs; prospective; public health priorities; racial and ethnic; response; sample collection; stem; tool; trimethyloxamine

PROJECT SUMMARY/ABSTRACT This K01 Career Development Award proposes a multidisciplinary 4-year training program to provide the candidate, Dr. Yeyi Zhu, with the experience and resources necessary to launch a successful career as an independent investigator to elucidate early origins of obesity and related comorbidities. The childhood obesity epidemic remains an urgent public health priority. Early prevention is critical to stemming the tide of obesity. Yet, our ability to identify promising prevention targets has been impeded by the difficulty in measuring the holistic metabolic status by conventional tools. Several human studies, including from Dr. Zhu's previous work, indicate that individual exposures including dietary factors in pregnancy may program obesity risk in later life. However, the underlying metabolic pathways are elusive. To fill this important knowledge gap, Dr. Zhu will use a novel holistic framework that leverages both targeted and untargeted metabolomics approach, the state-of- the-art electronic health records (EHR) data, and bioinformatics analytics to investigate the mechanisms by which the in-utero environment may infer risk of fetal growth extremes [small for gestational age (SGA) or large for gestational age (LGA)] and altered infant growth trajectories and excess adiposity (weight-for-length or body- mass-index-for-age z-score ≥85th percentile). This application takes advantage of the Pregnancy Environment and Lifestyle Study within Kaiser Permanente Northern California, with unique, robust resources of fasting serum specimens collection in early to mid-pregnancy, anthropometric measurements, multi-domain survey data (e.g., diet, physical activity, psychosocial assessments), and EHR data throughout the gestation and offspring infancy. The specific aims, to be examined in a sample of 150 LGA, 150 SGA, and 150 appropriate for gestational age births, are to: examine the associations between candidate (branch-chain amino acids, myo-inositol, trimethylamine N-oxide, acylcarnitines, and fatty acids) and untargeted metabolites in early to mid-pregnancy with fetal growth extremes (Aim 1) and infant growth trajectories and excess adiposity from 0-2 years (Aim 2), and explore metabolomic signatures for dietary factors in utero (Aim 3). Study findings may elucidate the underlying metabolic pathways and potential upstream preventive targets related to modifiable in- utero exposures, such as maternal dietary factors, to mitigate childhood obesity. Dr. Zhu is well suited to perform this research: 1) she has a solid foundation in epidemiology, nutrition, and biostatistics; 2) this K01 will significantly broaden her repertoire of advanced training in metabolomics, bioinformatics, and related biological interpretation; and 3) she has leveraged a carefully coordinated set of resources including a multidisciplinary mentorship committee, coursework, and applied learning closely aligned with the training objectives and specific aims. This K01 is essential to advance her long-term career objective of becoming an independent investigator with expertise in omics and bioinformatics to study early origins of cardiometabolic disease, with the ultimate goal to inform individualized care for upstream prevention of obesity and its comorbidities.

项目摘要/摘要 该K01职业发展奖提案提案一项多学科的4年培训计划，旨在提供 候选人Yeyi Zhu博士，拥有成功职业生涯所必需的经验和资源 独立研究者阐明肥胖和相关合并症的早期起源。童年肥胖 流行仍然是紧急的公共卫生优先事项。早期预防对于阻止肥胖的潮流至关重要。 然而，我们确定预防目标的能力受到了测量困难的困难 传统工具的整体代谢状态。一些人类研究，包括朱博士以前的工作 表明包括怀孕中饮食因素在内的个人暴露可能会在以后的生活中对肥胖风险进行规划。 但是，潜在的代谢途径难以捉摸。为了填补这个重要的知识差距，朱博士将使用 一个新型的整体框架，利用针对性和不靶向代谢组学方法，即 ART电子健康记录（EHR）数据和生物信息学分析，以研究机制 Utero环境可能会推断出极端胎儿生长的风险[妊娠年龄（SGA）或大型 对于胎龄（LGA）]和婴儿生长轨迹的改变并超过肥胖（重量或体重 - 质量指数的z得分≥85％）。该应用利用怀孕环境 和北加州凯撒（Kaiser Permanente）的生活方式研究，并拥有独特，强大的禁食资源 血清标本收集早期至中期，人体测量值，多域调查 数据（例如，饮食，体育锻炼，社会心理评估）和EHR数据在整个妊娠期间 后代婴儿期。具体目标，将在150 LGA，150 SGA和150个适当的样本中进行检查 对于胎龄出生，要：检查候选者之间的关联（分支链氨基酸， 肌醇，三甲胺N-氧化物，酰基肉碱和脂肪酸）和未靶向的代谢物早期至 胎儿生长极端（AIM 1）和婴儿生长轨迹的怀孕中期，超过0-2 年（AIM 2），并探索子宫内饮食因素的代谢组学特征（AIM 3）。研究结果可能 阐明基本的代谢途径和潜在的上游预防目标 子宫暴露，例如饮食因素，以减轻儿童肥胖症。朱博士非常适合 进行这项研究：1）她在流行病学，营养和生物统计学方面具有坚实的基础； 2）这个K01将 显着扩大了她对代谢组学，生物信息学和相关生物学的高级培训的曲目 解释; 3）她利用了一套精心协调的资源，包括多学科 指导委员会，课程和应用学习与培训目标紧密一致 具体目标。这个K01对于促进她成为独立的长期职业目标至关重要 研究人员具有OMICS和生物信息学专业知识，以研究心脏代谢疾病的早期起源， 为个性化护理提供肥胖及其合并症上游预防的个性化护理的最终目标。