Dietary Fructose and Redox Effects in Pediatric Nonalcoholic Fatty Liver Disease

膳食果糖和氧化还原对小儿非酒精性脂肪肝的影响

• 批准号: 8122141
• 负责人: MIRIAM B. VOS
• 金额: $ 17.41万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-20 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8122141
• 关键词: Acute; Adult; Affect; Age; American; Animal Model; Animals; Area Under Curve; Beverages; Biochemistry; Biopsy; Calories; Carbohydrates; Central obesity; Child; Child Nutrition; Childhood; Chronic; Consumption; Controlled Study; Cysteine; Cystine; Cytokeratin 18; Data; Development; Diet; Dietary Intervention; Disease; Double-Blind Method; Dyslipidemias; Epidemic; Ethnic Origin; Fatty Liver; Fatty acid glycerol esters; Fructose; Future; Gender; Glucose; Glutathione Disulfide; Goals; Health; Hepatic; Hepatocyte; Human; Hyperlipidemia; Hypertension; Hypertriglyceridemia; Image; Inflammation; Ingestion; Institution; Insulin Resistance; Intake; Intervention; Knowledge; Lead; Lipids; Liver; Liver diseases; Magnetic Resonance Imaging; Master of Science; Measures; Mediating; Mentors; Methodology; Monosaccharides; National Health and Nutrition Examination Survey; Natural History; Necrosis; Nonesterified Fatty Acids; Nuclear Magnetic Resonance; Nutrient; Obesity; Oral; Overweight; Oxidation-Reduction; Oxidative Stress; Pathogenesis; Pathologic; Physicians; Plasma; Play; Prevention; Principal Investigator; Public Health; Race; Randomized; Recommendation; Reporting; Research; Research Design; Research Personnel; Role; Scientist; Source; Stable Isotope Labeling; Staging; Surveys; Sweetening Agents; Techniques; Tracer; Training; Translational Research; Triglycerides; United States; Weight; carbohydrate metabolism; cohort; effective intervention; experience; improved; indexing; innovation; intrahepatic; lipid biosynthesis; non-alcoholic fatty liver; nonalcoholic steatohepatitis; novel; nutrition; obesity treatment; oxidized low density lipoprotein; response; stable isotope; sugar; sweetened beverage

DESCRIPTION (provided by applicant): Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease closely associated with obesity and insulin resistance. Because of the obesity epidemic, NAFLD has become the most common liver disease in children and adults. Extrapolating from adult natural history studies, in the next several decades, NAFLD may cause end-stage liver disease in over 150,000 of today's children. In the United States, caloric sweetener consumption has increased dramatically over the past 3 decades resulting in higher daily consumption of fructose, a monosaccharide that is metabolized primarily in the liver. In animal models, fructose induces fatty liver as well as hyperlipidemia, oxidative stress, obesity and hypertension. Thus, fructose-induced fatty liver closely mimics features of human NAFLD. It is unknown if fructose induces fatty liver, dyslipidemia and oxidative stress in children. We hypothesize that dietary fructose plays a critical role in the induction of NAFLD in susceptible obese children. The long range goal is to improve health by optimizing nutrition in the prevention and treatment of obesity-associated pediatric NAFLD. The objective of these specific studies is to determine if dietary fructose increases plasma triglycerides and oxidative stress in children with NAFLD. These studies are innovative as fructose has not been studied in children with NAFLD despite the fact that children have a high consumption of fructose. These results will be significant for public health because fructose consumption is pervasive and could be modified to improve health on a societal level. The applicant is a pediatric hepatologist who has completed a Masters of Science in Public Health She is an outstanding candidate with a proven focus of research in pediatric NAFLD and nutrition. She is mentored by two senior investigators with extensive experience in translational research and nutrition relevant to these studies. Future training in biochemistry, nutrition, stable isotope tracer studies and novel hepatic and metabolite imaging is planned. This mentored research experience will facilitate her development into a successful independent physician scientist. PUBLIC HEALTH RELEVANCE: This research will improve knowledge about the role of fructose in pediatric nonalcoholic fatty liver disease, a disease that affects over 3 million children in the United States. These studies are designed to lead to improved treatment and prevention of NAFLD in children, thus improving the health of millions of children.

描述（由申请人提供）： 非酒精性脂肪肝病（NAFLD）是一种与肥胖和胰岛素抵抗密切相关的慢性肝病。由于肥胖流行，NAFLD 已成为儿童和成人中最常见的肝脏疾病。根据成人自然史研究推断，在未来几十年内，NAFLD 可能会导致当今超过 150,000 名儿童出现终末期肝病。在美国，过去三十年中热量甜味剂的消耗量急剧增加，导致果糖（一种主要在肝脏代谢的单糖）的每日消耗量增加。在动物模型中，果糖会诱发脂肪肝以及高脂血症、氧化应激、肥胖和高血压。因此，果糖诱导的脂肪肝与人类 NAFLD 的特征非常相似。目前尚不清楚果糖是否会诱发儿童脂肪肝、血脂异常和氧化应激。我们假设膳食果糖在易感肥胖儿童诱发 NAFLD 中发挥着关键作用。长期目标是通过优化营养来预防和治疗与肥胖相关的儿科 NAFLD，从而改善健康。这些具体研究的目的是确定膳食果糖是否会增加 NAFLD 儿童的血浆甘油三酯和氧化应激。这些研究具有创新性，因为尽管儿童摄入了大量果糖，但尚未对患有 NAFLD 的儿童进行果糖研究。这些结果对公共卫生具有重要意义，因为果糖消费非常普遍，并且可以通过修改来改善社会层面的健康。申请人是一名儿科肝病学家，已完成公共卫生理学硕士学位。她是一位杰出的候选人，在儿科 NAFLD 和营养方面的研究已得到证实。她由两名高级研究人员指导，他们在与这些研究相关的转化研究和营养方面拥有丰富的经验。未来计划开展生物化学、营养学、稳定同位素示踪剂研究以及新型肝脏和代谢物成像方面的培训。这种受指导的研究经验将有助于她发展成为一名成功的独立医师科学家。 公共健康相关性：这项研究将提高人们对果糖在儿科非酒精性脂肪肝中的作用的认识，这种疾病影响着美国超过 300 万儿童。这些研究旨在改善儿童 NAFLD 的治疗和预防，从而改善数百万儿童的健康。