Biobehavioral and Environmental Contributions to Metabolomic Profiles and Early Life Body Composition

生物行为和环境对代谢组学特征和生命早期身体成分的贡献

基本信息

批准号：
10669244
负责人：
Lacey W. Heinsberg
金额：
$ 13.51万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10669244
关键词：
Address Adult Age Alleles Amino Acids Beginning of Life Behavior Behavioral Biochemical Biological Birth Blood Body Composition Body mass index Bone Density CREB3 gene Carbon Cell model Cessation of life Child Childhood Chronic Clinical Cohort Studies Communities Competence Complex Data Data Analyses Data Collection Dedications Development Diabetes Mellitus Diet Disease Dryness Dual-Energy X-Ray Absorptiometry Environment Environmental Risk Factor Etiology Fatty acid glycerol esters Foundations Future Genetic Genetic Variation Genotype Geography Goals Growth Health Infant Intervention Knowledge Life Lipids Longevity Maternal and Child Health Measures Mentors Mentorship Metabolic Metabolic Pathway Methodology Methods Minor Minority Groups Mothers Mus Nonesterified Fatty Acids Obesity Obesity associated disease Pacific Islander Participant Pathway interactions Phase Phenotype Population Pre-Clinical Model Public Health Quality of life Research Research Personnel Resources Risk Risk Factors Role Samoa Samoan Sampling Sleep Socioeconomic Status Spottings Symptoms Thinness Time Training Translating Umbilical Cord Blood Underrepresented Minority Underrepresented Populations Variant Weight Work biobehavior bone bone mass cardiometabolism career development cohort design ethnic diversity experience health equity high risk high risk population improved infancy insight metabolomics nutrition obesity in children obesity prevention obesity risk phenotypic data precision medicine premature prenatal prevent programs racial diversity risk variant

项目摘要

ABSTRACT: Childhood obesity is a significant public health problem and key risk factor for chronic conditions in adulthood. As such, there is critical need to understand childhood obesity etiology and identify opportunities for the earliest possible interventions to promote wellness across the lifespan. To that end, the objective of this proposal is to use metabolomics to better understand the foundations of variation in adiposity and body composition (e.g., fat mass, lean mass, bone mass, weight-for-age) in infancy and early life. The long-term training goal of this project is to support Dr. Heinsberg in becoming an independent investigator with a program of research dedicated to understanding and preventing obesity and improving maternal/child health. The mentored K99 will focus on participants from the nation of Samoa, as Pacific Islanders have the highest risk of obesity-related complications in the world, are one of the fastest-growing U.S. populations, but are underrepresented in health research. In Pacific Islander adults, a missense variant (rs373863828) in CREB3 Regulatory Factor (CREBRF) has an effect on body mass index larger than any other common variant. Paradoxically, the obesity-risk allele is protective against diabetes, making its functional role unclear and necessitating further mechanistic study before intervention can be considered. The obesity phenotypes of the variant are not present at birth but present clinically later in childhood. Given the results of CREBRF pre-clinical modeling and our preliminary work in infants, we hypothesize that the biological effects of the variant are present much earlier in life. To investigate this hypothesis, the K99 will draw from the Foafoaga o le Ola (“Beginning of Life”) Samoan infant cohort study. Existing resources include infant CREBRF genotype data, biospecimens, and body composition measured using dual-energy X-ray absorptiometry as well as rich behavioral/environmental data for mother-infant dyads at 1 week, 4 months, and 20 months post-birth. We will use temporal, untargeted metabolomics to increase our understanding of the biochemical mechanisms of the CREBRF variant with an emphasis on behavior/environment (Aim 1) and the foundations of body composition over the first two years of life (Aim 2). The results are expected to provide knowledge that can be translated to improved child wellness and health equity in Samoa and Pacific Islander communities in the U.S. With access to existing biospecimens and rich data from a geographically isolated birth cohort, unparalleled mentorship, and superb resources, the training environment is truly outstanding. K99 training goals to support the transition to independence include (1) metabolomic data collection/analysis, (2) metabolomic data interpretation in obese phenotypes, (3) conduct of childhood obesity research in underrepresented groups, and (4) career development. In the R00, the K99 methods will be applied to study early life adiposity in a more diverse sample (Aim 3). The insights gained will provide critical context for future work to prevent childhood obesity, promote wellness, and optimize precision medicine for public health.

摘要：儿童肥胖是一个重大的公共卫生问题，也是慢性病的关键危险因素因此，迫切需要了解儿童肥胖的病因并找出机会。尽早采取干预措施以促进整个生命周期的健康。建议利用代谢组学来更好地了解肥胖和身体变化的基础婴儿期和生命早期的成分（例如脂肪量、瘦肉量、骨量、年龄别体重）。该项目的培训目标是支持海因斯伯格博士成为一名独立调查员并制定计划致力于了解和预防肥胖以及改善孕产妇/儿童健康的研究。受指导的 K99 将重点关注萨摩亚国家，因为太平洋岛民的感染风险最高世界上与肥胖相关的并发症是美国人口增长最快的问题之一，但在太平洋岛民成年人中，CREB3 中存在错义变异 (rs373863828)。调节因子 (CREBRF) 对体重指数的影响比任何其他常见变量都大。矛盾的是，肥胖风险等位基因可以预防糖尿病，但其功能作用尚不清楚，而且可以考虑在干预之前进行进一步的机制研究。鉴于 CREBRF 临床前的结果，该变异在出生时不存在，但在儿童后期临床上存在。通过对婴儿的建模和初步工作，我们发现该变异的生物学效应是为了研究这一假设，K99 将从 Foafoaga o le Ola 中汲取灵感。（“生命之初”）萨摩亚婴儿队列研究包括婴儿 CREBRF 基因型数据、使用双能 X 射线吸收法测量生物样本和身体成分以及丰富的我们将提供母婴二人在出生后 1 周、4 个月和 20 个月时的行为/环境数据。使用时间、非靶向代谢组学来增加我们对生物化学机制的理解 CREBRF 变体强调行为/环境（目标 1）和身体成分的基础生命的头两年（目标 2）。改善美国萨摩亚和太平洋岛民社区的儿童健康和健康公平现有的生物样本和来自地理上孤立的出生队列的丰富数据，无与伦比的指导，以及一流的资源，真正出色的培训环境支持K99培训目标的转型。独立性包括（1）代谢组数据收集/分析，（2）肥胖代谢组数据解释表型，(3) 在代表性不足的群体中进行儿童肥胖研究，以及 (4) 职业在 R00 的开发中，K99 方法将用于研究更多样化样本中的早期肥胖。（目标 3）。获得的见解将为未来预防儿童肥胖、促进儿童肥胖的工作提供重要背景。健康，并优化公共卫生的精准医疗。