Lifecourse dietary exposures and offspring hepatic fat in early childhood: a nutrigenomic approach

生命历程中的饮食暴露和幼儿期的后代肝脂肪：营养基因组学方法

基本信息

批准号：
10737605
负责人：
Catherine Cioffi Cohen
金额：
$ 2.95万
依托单位：
UNIVERSITY OF COLORADO DENVER
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：
2022-05-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10737605
关键词：
Address Adolescence Age Applications Grants Area Attenuated Award Birth Breast Feeding Child Child Nutrition Childhood Clinical Management Clinical Research Clinical Treatment Colorado Data Deposition Development Diagnosis Diet Dietary Intervention Dietitian Disease Doctor of Philosophy Early Diagnosis Energy Intake Enrollment Ensure Exposure to Fatty acid glycerol esters Fellowship Fiber Fibrosis Foundations Functional disorder Future Genetic Genetic Carriers Genetic Risk Genomics Genotype Goals Grant Health Hepatic Hispanic Infant Interview Joints K-Series Research Career Programs Knowledge Life Life Cycle Stages Link Liquid substance Liver Magnetic Resonance Imaging Measures Mediating Mediation Medical Metabolic Modeling Modification Mothers Nutritional Obesity Onset of illness Pathogenesis Patients Population Pregnancy Productivity Proteins Puberty Publishing Research Research Institute Research Personnel Resources Risk Risk Factors Role Sampling Scientist Severity of illness Steatohepatitis Subgroup Testing Training Translating Translational Research Universities Visit cardiometabolism career chronic liver disease clinical translation cohort design dietary disease diagnosis disorder prevention disorder risk early childhood experience gene interaction genetic risk factor in utero infancy innovation insight longitudinal analysis maternal diabetes maternal obesity mother nutrition non-alcoholic fatty liver disease nutrition nutrition related genetics nutritional genomics obesity in children obesogenic offspring pediatric non-alcoholic fatty liver disease postnatal prenatal prenatal exposure prevent programs risk variant saturated fat skills success sugar

项目摘要

PROJECT SUMMARY/ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and carries substantial metabolic and liver-related health risks. Although NAFLD is commonly diagnosed in adolescence, around or after pubertal onset, patients can have varying disease severity at diagnosis, with some having steatohepatitis or advanced fibrosis, suggesting that disease pathogenesis begins much earlier than diagnosis, but is “silent”. From a nutrition perspective, it’s critical that we examine dietary risk factors associated with hepatic fat, especially early on in its development, to better understand the optimal dietary targets and timing for disease prevention. To address this knowledge gap, the proposed research will leverage data/samples from the Healthy Start Study, a longitudinal pre-birth cohort in Colorado that has followed ~1,400 mother-child dyads from pregnancy through early childhood. The specific aims are to: (1) examine independent associations of dietary exposures during distinct lifestages (in utero, infancy, and childhood) with longitudinal hepatic fat from 4-10 yrs; (2) assess the joint and mediating effects of multiple lifecourse dietary exposures on childhood hepatic fat; (3) evaluate whether genetic risk factors for NAFLD modify diet-hepatic fat associations. The central hypothesis is that obesogenic dietary exposures throughout the lifecourse will predict higher hepatic fat deposition in early childhood and that associations will differ in carriers of genetic risk alleles for NAFLD compared to non-carriers. The applicant is a productive PhD scientist and Registered Dietitian, and her long-term career goal is to establish an independent research program that investigates associations of nutritional exposures with pediatric NAFLD risk and severity, and then translates these findings into effective nutrition interventions for preventing NAFLD. To further this goal and to achieve the proposed research aims, the applicant has developed a comprehensive training plan, which will be a logical expansion of her prior background/training and includes the following goals: 1) gain knowledge/skills in lifecourse research and longitudinal analysis; 2) gain knowledge/skills in genomics and nutrigenetics; 3) build expertise in the developmental origins and clinical treatment of pediatric NAFLD; 4) gain experience designing and managing clinical research; 5) enhance research network and professional skills. The University of Colorado Denver-Anschutz Medical Campus is an outstanding research institute with the resources and collaborators needed to facilitate the applicant’s training in these areas. The findings generated from this proposal will generate preliminary data to serve as the foundation for future grant applications, including a career development award, during which the applicant will pursue both observational and clinical-translational research aiming to advance our understanding of the lifecourse determinants and consequences of pediatric NAFLD. Collectively, the proposed research and training will enable the applicant to strategically expand her knowledge, skills, and expertise, and facilitate her transition to independent pediatric nutrition researcher.

项目摘要/摘要非酒精性脂肪肝病（NAFLD）是儿童中最常见的慢性肝病大量代谢和肝有关的健康风险通常在青春期被诊断出在青春期发作周围或之后，患者在诊断时可能会有不同的疾病严重程度，其中一些患者患有脂肪性肝炎或晚期纤维化，表明病原体开始比诊断早得多但从营养角度来看，我们是“沉默” 脂肪，尤其是在其发展的早期，以更好地了解最佳饮食目标和疾病的时机预防，以解决这一知识差距，从健康中支撑的研究数据/样本。开始研究，科罗拉多州的纵向出生前队列，遵循约1,400个母子二元。通过幼儿期的怀孕。在4-10岁的纵向肝脂肪中，在不同的生命周期（子宫，婴儿期和童年时期）暴露；（2）评估多种生命的饮食暴露对儿童期肝脂肪的关节和中介作用；（3）评估NAFLD模拟脂肪关联的遗传危险因素。肥胖的饮食暴露这种生命力将预测早期的肝发作性疲劳较高与非携带者相比，NAFLD的遗传风险等位基因携带者的童年和统计会有所不同。申请人是一位富有成效的博士科学家和注册营养师，她的长期职业目标是建立一项独立的研究计划，该计划将营养暴露与小儿NAFLD的关联风险和过渡，以及这些联合会进入eTtings营养干预措施，以防止NAFLD。为了进一步实现这一目标并实现拟议的研究目的，申请人已建立了一个全面的培训计划将是她先前背景/培训的逻辑扩展，并包括以下目标： 1）获得生命力研究和纵向分析的知识/技能； 2）获得基因组学知识/技能 3）在儿科NAFLD的发育起源和临床信托中建立专业知识；获得设计和管理临床研究的经验； 5）增强研究网络和专业技能。科罗拉多大学丹佛 - 阿斯丘茨医学校园是一家出色的研究所资源和合作者需要促进申请人在这些领域的培训从该提案中将生成预预制作数据，以作为未来赠款应用程序的基础职业发展奖，在此期间，申请人将同时伪造观察和奉献奖旨在提高我们对生命力的理解的研究阻止了儿科的决定因素和同意。 nafld。知识，技能和专业知识，并促进她向独立研究者的过渡。