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

生命历程中的饮食暴露和幼儿期的后代肝脂肪：一种营养方法

• 批准号: 10771627
• 负责人: Catherine Cioffi Cohen
• 金额: $ 0.25万
• 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/10771627
• 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; 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.

项目概要/摘要 非酒精性脂肪性肝病（NAFLD）是儿童中最常见的慢性肝病， 重大代谢和肝脏相关的健康风险。尽管 NAFLD 通常在青春期被诊断出来， 在青春期开始前后，患者在诊断时可能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，表明疾病发病机制比诊断早得多， 却是“沉默”。从营养角度来看，我们检查与肝病相关的饮食风险因素至关重要 脂肪，特别是在其发育早期，以更好地了解最佳饮食目标和疾病发生时间 预防。为了解决这一知识差距，拟议的研究将利用来自健康研究的数据/样本 Start Study 是科罗拉多州的一个纵向产前队列，追踪了约 1,400 名母子夫妇 怀孕到幼儿期。具体目标是：（1）检查饮食与饮食之间的独立关联。 在不同的生命阶段（子宫内、婴儿期和儿童期）暴露于 4-10 岁的纵向肝脂肪； (2) 评估多种生命全程饮食暴露对儿童肝脂肪的联合和中介效应； (3) 评估 NAFLD 的遗传风险因素是否会改变饮食与肝脂肪的关联。中心假设是 整个生命过程中的致肥胖饮食暴露将预测早期肝脏脂肪沉积较高 与非携带者相比，NAFLD 遗传风险等位基因携带者的关联会有所不同。 申请人是一位多产的博士科学家和注册营养师，她的长期职业目标是建立 一项独立研究计划，调查营养暴露与儿童 NAFLD 之间的关系 风险和严重程度，然后将这些发现转化为预防 NAFLD 的有效营养干预措施。 为了进一步实现这一目标并实现拟议的研究目标，申请人开发了全面的 培训计划，这将是她之前的背景/培训的逻辑扩展，包括以下目标： 1）获得生命历程研究和纵向分析的知识/技能； 2）获得基因组学知识/技能 和营养遗传学； 3) 建立儿科 NAFLD 的发育起源和临床治疗方面的专业知识； 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。 科罗拉多大学丹佛安舒茨医学校区是一所杰出的研究机构， 促进申请人在这些领域的培训所需的资源和合作者。产生的结果 根据该提案将生成初步数据，作为未来赠款申请的基础，包括 职业发展奖，在此期间申请人将追求观察和临床转化 旨在增进我们对儿科生命历程决定因素和后果的理解的研究 非酒精性脂肪性肝病。总的来说，拟议的研究和培训将使申请人能够战略性地扩展她的能力 知识、技能和专业知识，并促进她过渡为独立的儿科营养研究员。