Dietary factors, biomarkers, metabolic pathways related to non-alcoholic fatty liver disease

与非酒精性脂肪肝相关的饮食因素、生物标志物、代谢途径

• 批准号: 9223315
• 负责人: Jiantao Ma
• 金额: $ 24.9万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-05 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9223315
• 关键词: Advisory Committees; Advisory Committees; Affect; Affect; Aging; Aging; Area; Area; Atherogenic Diet; Atherogenic Diet; Award; Award; Biological Markers; Biological Markers; Biomedical Research; Biomedical Research; Biopsy; Biopsy; Boston; Boston; Carbohydrates; Carbohydrates; Cardiovascular Diseases; Cardiovascular Diseases; Cardiovascular system; Cardiovascular system; Career Choice; Career Choice; Career Transition Award; Career Transition Award; Characteristics; Characteristics; Chronic Disease; Chronic Disease; Cohort Studies; Cohort Studies; Collaborations; Collaborations; Collection; Collection; Committee Members; Committee Members; Communication; Communication; Communities; Communities; Complex; Complex; Counseling; Counseling; DNA Methylation; DNA Methylation; Data; Data; Data Analyses; Data Analyses; Data Collection; Data Collection; Development Plans; Development Plans; Diagnosis; Diagnosis; Diet; Diet; Dietary Factors; Dietary Factors; Dietary Practices; Dietary Practices; Disease; Disease; Disease Outcome; Disease Outcome; Eating; Eating; Educational process of instructing; Educational process of instructing; Educational workshop; Educational workshop; Epidemiology; Epidemiology; Extramural Activities; Extramural Activities; Family suidae; Family suidae; Foundations; Foundations; Framingham Heart Study; Framingham Heart Study; Funding; Funding; Future; Future; Gene Expression; Gene Expression; Genes; Genes; Genomics; Genomics; Goals; Goals; Gold; Gold; Grant; Grant; Heart; Heart; Histologic; Histologic; Histology; Histology; Human; Human; Intake; Intake; International; International; Intervention Studies; Intervention Studies; K22 Award; K22 Award; Knowledge; Knowledge; Laboratories; Laboratories; Leadership; Leadership; Link; Link; Liver; Liver; Liver Fibrosis; Liver Fibrosis; Mediating; Mediating; Medicine; Medicine; Mentored Clinical Scientist Development Award (K08); Mentored Clinical Scientist Development Award (K08); Mentors; Mentors; Metabolic; Metabolic; Metabolic Pathway; Metabolic Pathway; Methylation; Methylation; Molecular; Molecular; Molecular Epidemiology; Molecular Epidemiology; National Heart, Lung, and Blood Institute; National Heart, Lung, and Blood Institute; Non-Insulin-Dependent Diabetes Mellitus; Non-Insulin-Dependent Diabetes Mellitus; Nonpharmacologic Therapy; Nutrition Policy; Nutritional Science; Nutritional Science; Nutritional Study; Nutritional Study; Observational Study; Observational Study; Participant; Participant; Pathogenesis; Pathogenesis; Pathway interactions; Pathway interactions; Pattern; Pattern; Pharmacotherapy; Pharmacotherapy; Phase; Phase; Polyunsaturated Fatty Acids; Polyunsaturated Fatty Acids; Population Sciences; Population Sciences; Postdoctoral Fellow; Postdoctoral Fellow; Preparation; Preparation; Prevention; Prevention; Prevention strategy; Prevention strategy; Primary Prevention; Primary Prevention; Public Health Schools; Public Health Schools; Randomized; Randomized; Randomized Controlled Trials; Randomized Controlled Trials; Recommendation; Recommendation; Research; Research; Research Institute; Research Institute; Research Personnel; Research Personnel; Risk; Risk; Risk Factors; Risk Factors; Sampling; Sampling; Saturated Fatty Acids; Saturated Fatty Acids; Schools; Schools; Science Policy; Scientist; Scientist; Senior Scientist; Senior Scientist; Severities; Severities; Sodium; Sodium; Statistical Methods; Statistical Methods; Techniques; Techniques; Testing; Testing; Training; Training; Universities; Universities; Whole Blood; Whole Blood; Work; Work; Writing; Writing; base; base; cardiometabolism; cardiovascular disorder epidemiology; cardiovascular disorder epidemiology; career; career; career development; career development; data management; data management; design; design; epidemiology study; epidemiology study; epigenetic marker; epigenetic marker; feeding; feeding; follow-up; follow-up; good diet; good diet; high risk; high risk; insight; insight; medical schools; medical schools; methylome; methylome; multidisciplinary; multidisciplinary; non-alcoholic fatty liver; non-alcoholic fatty liver disease; noninvasive diagnosis; noninvasive diagnosis; novel; novel; nutrition; nutrition; population based; population based; prevent; prevent; professor; professor; programs; programs; prospective; prospective; research and development; research and development; screening; screening; skills; skills; training opportunity; training opportunity; treatment strategy; treatment strategy

Project Summary/Abstract Non-alcoholic fatty liver disease (NAFLD) is an important risk factor of type 2 diabetes and cardiovascular disease (CVD). This proposed project will study the association between dietary patterns and NAFLD in participants of the Framingham Heart Study (FHS), a large population-based cohort study (Aim 1). In addition, this project will examine the whole blood-derived DNA methylation signatures associated with dietary patterns and NAFLD in FHS participants (Aim 2). Diet related DNA methylation signatures in the liver will be examined using samples collected from an existing randomized, controlled experimental trial in Ossabaw pigs (Aim 3). Completion of the proposed project will provide evidence for dietary recommendations designed specifically to prevent NAFLD. Second, it will identify epigenetic biomarkers of NAFLD and its severity. Third, information generated from this project will contribute to a better understanding of the molecular pathways linking diet and NAFLD, and will serve as a basis for future prevention and treatment strategies. The candidate, Dr. Jiantao Ma, is currently a postdoctoral fellow at NHLBI’s Population Sciences Branch, headed by Dr. Daniel Levy. Dr. Levy is also the Director of the FHS and will serve as the primary mentor in Dr. Ma’s Advisory Committee. The Branch has a longstanding, impressive record of conducting large epidemiologic studies of CVD and other disease outcomes, and an outstanding track record of successfully training young investigators. The Advisory Committee also includes two internationally recognized experts in nutrition and epidemiology, Dr. Frank B. Hu, Professor of Nutrition and Epidemiology at Harvard T.H. Chan School of Public Health (HSPH) and Professor of Medicine at Harvard Medical School, and Dr. Alice H. Lichtenstein, Senior Scientist and Director of the Cardiovascular Nutrition Laboratory at Jean Mayer USDA Human Nutrition Research Center on Aging and Stanley N. Gershoff Professor of Nutrition Science and Policy of the Friedman School of Nutrition Science and Policy at Tufts University. Through this K22 Career Transition Award proposal, Dr. Ma seeks to systematically acquire additional mentored research and career development training at NHLBI. With the support from his Advisory Committee members, the K22 award will establish a training framework to initiate the research program in preparation for his independent career. As detailed in the Career Development Plan, new scientific skills that will be acquired include general training in genomics, techniques regarding data collection and management, and advanced statistical methods for complex omics data analysis through a combination of specialized coursework and hands-on training. The scientific training will support Dr. Ma to complete the proposed studies outlined in the Research Strategy. This will serve as the foundation for Dr. Ma’s future R01 grant and additional independent funding application upon his transition to independence. Dr. Ma will also participate in extensive career development training during the intramural mentored phase. Dr. Ma will be trained in mentoring, teaching, management, and leadership through courses, seminars, and workshops specifically developed for emerging junior investigators. In this phase of career development training, Dr. Ma will receive counselling on career paths in biomedical research, guidance on grant writing, and training on effective communication of scientific results to both the research and non-research communities. Dr. Ma’s Advisory Committee will evaluate his progress on the proposed research and career development training. This training opportunity will allow Dr. Ma to master knowledge and skills needed to become a well-rounded, multidisciplinary biomedical researcher in the extramural phase of this award and beyond. Dr. Ma’s long-term goal is to establish himself as an accomplished scientist and professor in a prestigious academic research institute, where he can study the pathogenesis of CVD and related chronic disease and to leverage results obtained in observational studies to implement in intervention studies for prevention and treatment of CVD. In summary, in this proposal for the NHLBI K22 Award, Dr. Ma will systematically examine dietary factors, biomarkers, and metabolic pathways related to NAFLD. With support from his Advisory Committee members and the K22 award, Dr. Ma will acquire additional scientific training, particularly in molecular epidemiology (DNA methylation and gene expression), and rich career development training. This training opportunity will facilitate Dr. Ma’s successful transition to become an independent investigator in the area of cardiovascular epidemiology.

项目总结/摘要 非酒精性脂肪性肝病（NAFLD）是2型糖尿病和心血管疾病的重要危险因素 疾病（CVD）。这项拟议的项目将研究饮食模式和非酒精性脂肪肝之间的联系， FHS是一项大型人群队列研究（Aim 1）。此外，本发明还提供了一种方法， 该项目将研究与饮食模式相关的全血DNA甲基化特征 FHS参与者的NAFLD（目标2）。将检查肝脏中与饮食相关的DNA甲基化特征 使用从Ossabaw猪的现有随机对照实验试验中收集的样品（目的3）。 拟议项目的完成将为专门设计的饮食建议提供证据， 预防NAFLD。其次，它将确定NAFLD及其严重程度的表观遗传生物标志物。三是信息 从这个项目产生的将有助于更好地了解分子途径连接饮食和 NAFLD，并将作为未来预防和治疗策略的基础。 候选人马建涛博士目前是NHLBI人口科学分支的博士后研究员， 由丹尼尔·利维博士领导利维博士也是FHS的主任，并将担任主要导师在博士。 马的顾问委员会。该分支长期以来在开展大型 心血管疾病和其他疾病结局的流行病学研究，以及成功的 培训年轻的调查员。咨询委员会还包括两名国际公认的专家， 营养学和流行病学，弗兰克B博士。哈佛大学营养与流行病学教授Hu说。陈 公共卫生学院（HSPH）、哈佛医学院医学教授和Alice H.博士。 美国农业部Jean Mayer心血管营养实验室高级科学家兼主任Lichelman说， 人类营养老化研究中心和斯坦利N。Gershoff营养科学与政策教授 他是塔夫茨大学弗里德曼营养科学与政策学院的教授。 通过这个K22职业转型奖的建议，马博士寻求系统地获得额外的 在NHLBI指导研究和职业发展培训。在其咨询委员会的支持下， 成员，K22奖将建立一个培训框架，以启动研究计划，为 独立的职业生涯。如职业发展计划中所述，将获得的新的科学技能 包括基因组学、数据收集和管理技术以及高级 通过专业课程的结合，复杂的组学数据分析的统计方法， 动手训练。科学培训将支持马博士完成 研究战略。这将作为马博士未来R 01赠款和额外独立研究的基础。 在他向独立过渡时提出资金申请。 博士马还将在校内辅导阶段参加广泛的职业发展培训。博士 马云将通过课程、研讨会和 专门为新出现的初级调查员举办讲习班。在职业发展的这个阶段 在培训期间，马博士将接受生物医学研究职业道路的咨询，撰写资助申请的指导， 关于向研究界和非研究界有效传播科学成果的培训。博士 马的顾问委员会将评估他在拟议的研究和职业发展培训方面的进展。 这个培训机会将使马博士掌握成为一个全面， 多学科生物医学研究人员在这个奖项的校外阶段和超越。马博士长期 我的目标是成为一名有成就的科学家和教授，从事著名的学术研究 研究所，在那里他可以研究CVD和相关慢性疾病的发病机制，并利用结果 在观察性研究中获得，用于预防和治疗CVD的干预研究。 总之，在这次NHLBI K22奖的提案中，马博士将系统地考察饮食因素， 生物标志物和与NAFLD相关的代谢途径。在咨询委员会成员的支持下， 和K22奖，马博士将获得额外的科学培训，特别是在分子流行病学 (DNA甲基化和基因表达），以及丰富的职业发展培训。这次培训机会将 帮助马博士成功转型为心血管领域的独立研究者， 流行病学