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: 10627605
• 负责人: Yeyi Zhu
• 金额: $ 4.74万
• 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 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10627605
• 关键词: Adult; Affect; Age; Area; Bioinformatics; Biological; Biological Markers; Biometry; Birth; Body mass index; Branched-Chain Amino Acids; California; Cardiometabolic Disease; Caucasians; Child; Clinical; Complement; Data; Data Collection; Diet; Dietary Factors; 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; career; comorbidity; dietary; experience; fetal; fetal programming; follow-up; gut microbiota; hands-on learning; high risk; human data; in utero; indexing; individualized prevention; infancy; metabolomics; mitochondrial dysfunction; multi-racial; 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.

项目概要/摘要 K01 职业发展奖提出了一个为期 4 年的多学科培训计划，以提供 候选人，Yeyi Zhu博士，拥有作为一名成功的职业生涯所需的经验和资源 独立研究者阐明肥胖和相关合并症的早期起源。儿童肥胖症 流行病仍然是紧迫的公共卫生优先事项。早期预防对于遏制肥胖浪潮至关重要。 然而，我们确定有希望的预防目标的能力因难以衡量 通过传统工具的整体代谢状态。几项人体研究，包括朱博士之前的工作， 表明怀孕期间的个人暴露（包括饮食因素）可能会影响以后生活中的肥胖风险。 然而，潜在的代谢途径是难以捉摸的。为了填补这一重要的知识空白，朱博士将使用 一个新颖的整体框架，利用靶向和非靶向代谢组学方法，状态 最先进的电子健康记录（EHR）数据和生物信息学分析来研究其机制 子宫内环境可能会推断胎儿生长极端的风险[小于胎龄 (SGA) 或大于胎龄 胎龄（LGA）]以及婴儿生长轨迹改变和过度肥胖（身高别体重或身体- 年龄质量指数 z 分数≥85%）。该应用程序利用怀孕环境 北加州凯撒医疗机构内的生活方式研究，拥有独特、强大的禁食资源 妊娠早中期血清标本采集、人体测量、多领域调查 数据（例如饮食、体力活动、社会心理评估）以及整个妊娠和妊娠期间的 EHR 数据 子孙幼年期。具体目标，以 150 个 LGA、150 个 SGA 和 150 个适当的样本进行检验 对于胎龄出生，应： 检查候选氨基酸（支链氨基酸、 肌醇、三甲胺 N-氧化物、酰基肉碱和脂肪酸）和早期至非目标代谢物 妊娠中期，胎儿生长极端（目标 1）和婴儿生长轨迹以及 0-2 岁过度肥胖 年（目标 2），并探索子宫内饮食因素的代谢组学特征（目标 3）。研究结果可能 阐明与可修改的in-相关的潜在代谢途径和潜在的上游预防目标 子宫内暴露，例如母亲饮食因素，以减轻儿童肥胖。朱博士非常适合 进行这项研究：1）她在流行病学、营养学和生物统计学方面有扎实的基础； 2）这个K01将 显着拓宽了她在代谢组学、生物信息学和相关生物学领域的高级培训范围 解释; 3）她利用了一系列精心协调的资源，包括多学科的资源 导师委员会、课程作业和应用学习与培训目标紧密结合 具体目标。这 K01 对于实现她成为独立人士的长期职业目标至关重要 具有组学和生物信息学专业知识的研究者，研究心脏代谢疾病的早期起源， 最终目标是为肥胖及其合并症的上游预防提供个性化护理。

项目成果

Longitudinal Plasma Metabolomics Profile in Pregnancy-A Study in an Ethnically Diverse U.S. Pregnancy Cohort.

• DOI: 10.3390/nu13093080
• 发表时间: 2021-09-01
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Mitro SD;Wu J;Rahman ML;Cao Y;Zhu Y;Chen Z;Chen L;Li M;Hinkle SN;Bremer AA;Weir NL;Tsai MY;Song Y;Grantz KL;Gelaye B;Zhang C
• 通讯作者: Zhang C

Plasma Acylcarnitines during Pregnancy and Neonatal Anthropometry: A Longitudinal Study in a Multiracial Cohort.

• DOI: 10.3390/metabo11120885
• 发表时间: 2021-12-17
• 期刊: Metabolites
• 影响因子: 4.1
• 作者: Song Y;Lyu C;Li M;Rahman ML;Chen Z;Zhu Y;Hinkle SN;Chen L;Mitro SD;Li LJ;Weir NL;Tsai MY;Zhang C
• 通讯作者: Zhang C

Plasma Phospholipid Monounsaturated Fatty Acids and Gestational Diabetes Mellitus: A Longitudinal Study in the NICHD Fetal Growth Studies-Singletons Cohort.

• DOI: 10.2337/db22-0241
• 发表时间: 2022-12-01
• 期刊: Diabetes
• 影响因子: 7.7

Longitudinal lipidomic profiles during pregnancy and associations with neonatal anthropometry: findings from a multiracial cohort.

• DOI: 10.1016/j.ebiom.2023.104881
• 发表时间: 2023-12
• 期刊: EBioMedicine
• 影响因子: 11.1