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

• 批准号: 10464241
• 负责人: Catherine Cioffi Cohen
• 金额: $ 7.18万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 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/10464241
• 关键词: Address; Adolescence; Age; Applications Grants; Area; Attenuated; Award; Birth; Breast Feeding; Child; Child Nutrition; Childhood; Clinical; 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; Future; Genetic; Genetic Carriers; Genetic Risk; Genomics; Genotype; Goals; Grant; Health; Hepatic; Hispanic; Infant; Interview; Joints; K-Series Research Career Programs; Knowledge; Link; Liquid substance; Liver; Magnetic Resonance Imaging; Measures; Mediating; Mediation; Medical; Metabolic; Modeling; Modification; Mothers; Nutritional; Obesity; Onset of illness; Pathogenesis; Patients; Population; Pregnancy; Proteins; Puberty; Publishing; Research; Research Institute; Research Personnel; Research Training; Resources; Risk; Risk Factors; Role; Sampling; Scientist; Severity of illness; Steatohepatitis; Subgroup; Testing; Training; Translating; Translational Research; Universities; Visit; cardiometabolism; career; chronic liver disease; cohort; design; dietary; 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

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 实质性的代谢和现场健康风险。尽管NAFLD通常在青少年中被诊断 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，表明疾病发病机理比诊断早得多 但是是“沉默”。从营养的角度来看，至关重要的是，我们检查与肝的饮食危险因素 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。为了解决这一知识差距，拟议的研究将利用健康的数据/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。 怀孕至幼儿。具体目的是：（1）检查饮食的独立关联 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）评估多种生命饮食暴露对童年肝脂肪的饮食饮食的关节和中介作用； （3） 评估NAFLD的遗传危险因素是否修改了饮食 - 肝脂肪的关联。中心假设是 在整个生命过程中，肥胖的饮食暴露将预测早期的肝脂肪沉积 与非携带者相比，NAFLD的童期和关联在NAFLD的遗传风险等位基因携带者方面会有所不同。 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 一个独立的研究计划，调查营养暴露与小儿NAFLD的关联 风险和严重程度，然后将这些发现转化为有效的营养干预措施，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，适用于 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）在生命力研究和纵向分析中获得知识/技能； 2）获得基因组学知识/技能 和营养材料； 3）在小儿NAFLD的发育起源和临床治疗方面建立专业知识； 4） 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 - 阿斯丘茨医学校区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。发现产生 从该建议中将生成初步数据，以作为未来赠款申请的基础，包括 职业发展奖，在此期间申请人将同时进行检查和临床翻译 旨在提高我们对生命的决定者和小儿后果的理解的研究 nafld。总的来说，拟议的研究和培训将使申请人能够从战略上扩大她 知识，技能和专业知识，并促进她向独立儿科营养研究人员的过渡。