Non-Alcoholic Fatty Liver Disease Ethnicity and Hepatic Metabolism

描述(由申请人提供)： 我是德克萨斯大学西南医学中心的胃肠病专家/肝病专家和内科助理讲师。我的长期目标是发展一个独立的职业生涯，成为一名翻译研究员，弥合基础科学应用和临床研究之间的差距。我对非酒精性脂肪性肝病(NAFLD)的流行病学和代谢基础感兴趣，尤其对这种疾病存在的种族差异感兴趣。当我对隐源性肝硬变和非酒精性脂肪肝之间的联系产生兴趣时，这个兴趣领域就发展起来了。我建议的职业发展计划结合了一个多学科计划，旨在提供紧张的、密切指导的、以患者为中心的研究经验，并结合临床研究中全面结构的教学课程。在医学博士Jay D.Morton和医学博士Craig Malloy的指导下，我将研究NAFLD的代谢基础。这项研究将利用稳定同位素技术结合核磁共振和气质联用技术来研究肝脏中间代谢，并将检验这一假说，即原发性NAFLD是多种代谢异常的结果，多个代谢表型与本病相关。这项研究将在达拉斯心脏研究的2287名受试者中进行，这些受试者的肝脏甘油三酯含量之前已经通过磁共振光谱进行了表征。这一队列中先前的一项研究表明，尽管NAFLD的危险因素(即肥胖、糖尿病、代谢综合征)的患病率相同，但非洲裔美国人和拉美裔美国人的肝脏脂肪变性的患病率存在显著差异。因此，这项研究的第二个目标将是确定肝脏代谢的种族差异，并将这些差异与发生肝脏脂肪变性的风险联系起来。

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.