Non-Alcoholic Fatty Liver Disease Ethnicity and Hepatic Metabolism

非酒精性脂肪肝的种族和肝脏代谢

• 批准号: 7448557
• 负责人: JEFFREY D BROWNING
• 金额: $ 13.26万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7448557
• 关键词: Accounting; Adult; African American; American; Arts; Basic Science; Cirrhosis; Citric Acid Cycle; Clinical Research; Cryptogenic cirrhosis; Development; Development Plans; Diabetes Mellitus; Disease; Doctor of Medicine; Educational Curriculum; Epidemiology; Ethnic Origin; European; Fatty Acids; Fatty Liver; Fatty acid glycerol esters; Fellowship; Functional disorder; Gas Chromatography; Gastroenterologist; General Population; Glucose; Glycerol; Glycogen; Goals; Heart; Hepatic; Hispanic Americans; Hispanics; Individual; Insulin Resistance; Internal Medicine; Lead; Lipolysis; Liver; Liver Function Tests; Liver Mitochondria; Liver diseases; Low Prevalence; Magnetic Resonance Spectroscopy; Mass Chromatography; Measurement; Measures; Medical center; Mentors; Mentorship; Metabolic; Metabolic syndrome; Metabolism; Mitochondria; Nuclear Magnetic Resonance; Obesity; Pharmaceutical Preparations; Pharmacologic Substance; Phenotype; Phosphoenolpyruvate; Phosphoenolpyruvate Carboxylase; Predisposition; Prevalence; Primary carcinoma of the liver cells; Protons; Pyruvate; Pyruvates; Race; Rate; Relative (related person); Research; Research Personnel; Risk; Risk Factors; Secondary to; Source; Spectrum Analysis; Structure; Techniques; Testing; Texas; Time; Triglycerides; Universities; base; career; cohort; design; ethnic difference; experience; glucose metabolism; glucose production; improved; in vivo; insight; instructor; interest; lipid biosynthesis; lipid metabolism; liver transplantation; non-alcoholic fatty liver; novel; oxidation; patient oriented research; programs; racial/ethnic difference; response; stable isotope

DESCRIPTION (provided by applicant): I am a gastroenterologist/hepatologist and Assistant Instructor in Internal Medicine at the University of Texas Southwestern Medical Center. My long-term goal is to develop an independent career as a translational researcher, bridging the gap between basic science applications and clinical research. I am interested in the epidemiology and metabolic basis of non-alcoholic fatty liver disease (NAFLD), with a special interest in the ethnic disparities that exist with this disease. This field of interest developed during fellowship when I became interested in the association between cryptogenic cirrhosis and NAFLD. My proposed career development plan incorporates a multi-disciplinary program designed to provide an intense, closely mentored, patient-oriented research experience in association with a comprehensively structured didactic curriculum in clinical research. Under the mentorship of Jay D. Morton, M.D. and Craig Malloy, M.D., I will investigate the metabolic basis of NAFLD. This research will focus on intermediary hepatic metabolism by using stable isotope techniques in combination with nuclear magnetic resonance and gas chromatography-mass spectroscopy and will test the hypothesis that primary NAFLD is the result of multiple metabolic abnormalities, with more than one metabolic phenotype being associated with this disease. The study will be conducted in a cohort of 2,287 subjects from the Dallas Heart Study whose liver triglyceride content has been previously characterized by magnetic resonance spectroscopy. A previous study in this cohort demonstrated significant differences in the prevalence of hepatic steatosis between African-Americans and Hispanics despite an equal prevalence of risk factors for NAFLD (i.e., obesity, diabetes, metabolic syndrome). Therefore, a second objective of this research will be to define ethnic differences in hepatic metabolism and relate these differences to the risk of developing hepatic steatosis.

描述（由申请人提供）： 我是得克萨斯大学西南医学中心的胃肠病学家/肝病学家和内科助理讲师。我的长期目标是发展一个独立的职业生涯作为一个翻译研究人员，弥合基础科学应用和临床研究之间的差距。我对非酒精性脂肪肝（NAFLD）的流行病学和代谢基础感兴趣，特别感兴趣的是这种疾病存在的种族差异。当我对隐源性肝硬化和NAFLD之间的联系感兴趣时，这个兴趣领域在研究期间发展起来。我提出的职业发展计划包括一个多学科的计划，旨在提供一个激烈的，密切指导，以病人为导向的研究经验，与全面结构的教学课程在临床研究。在Jay D的指导下，莫顿，医学博士和医学博士克雷格·马洛伊我将研究NAFLD的代谢基础。本研究将通过使用稳定同位素技术结合核磁共振和气相色谱-质谱法来关注中间肝脏代谢，并将测试原发性NAFLD是多种代谢异常的结果的假设，其中一种以上的代谢表型与这种疾病相关。本研究将在来自达拉斯心脏研究的2，287例受试者队列中进行，这些受试者的肝脏甘油三酯含量先前已通过磁共振波谱进行了表征。该队列中的先前研究表明，尽管NAFLD的风险因素的患病率相同，但非洲裔美国人和西班牙裔美国人之间的肝脂肪变性患病率存在显著差异（即，肥胖、糖尿病、代谢综合征）。因此，本研究的第二个目的是确定肝代谢的种族差异，并将这些差异与发生肝脂肪变性的风险联系起来。