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

基本信息

批准号：
8322772
负责人：
MIRIAM B. VOS
金额：
$ 17.34万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-20 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8322772
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 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 chronic liver disease cohort effective intervention experience improved indexing innovation intrahepatic lipid biosynthesis non-alcoholic fatty liver nonalcoholic steatohepatitis novel nutrition obesity in children obesity treatment oxidized low density lipoprotein response stable isotope sugar sweetened beverage

项目摘要

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病。从成人自然史研究中推断出来，在接下来的几十年中，NAFLD可能会在当今15万名儿童中引起末期肝病。在美国，在过去的三十年中，热量甜味剂的消耗量急剧增加，导致果糖的每日消耗量更高，果糖的每日消费量是一种主要在肝脏中代谢的单糖。在动物模型中，果糖会诱导脂肪肝以及高脂血症，氧化应激，肥胖和高血压。因此，果糖诱导的脂肪肝紧密模仿人NAFLD的特征。尚不清楚果糖是否诱导儿童脂肪肝，血脂异常和氧化应激。我们假设饮食果糖在敏感肥胖儿童的NAFLD诱导中起着至关重要的作用。远距离目标是通过在预防和治疗与肥胖相关的小儿NAFLD方面优化营养来改善健康。这些特定研究的目的是确定NAFLD儿童的饮食果糖是否增加了血浆甘油三酸酯和氧化应激。这些研究具有创新性，因为尽管儿童对果糖的食用量很高，但尚未在NAFLD儿童中研究果糖。这些结果对于公共卫生将很重要，因为果糖消耗普遍存在，并且可以修改以改善社会水平的健康。申请人是一名儿科肝病学家，已经完成了公共卫生科学硕士学位，她是一位杰出的候选人，在小儿NAFLD和营养方面具有良好的研究重点。她受到两位高级研究人员的指导，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。计划对未来的生物化学，营养，稳定的同位素示踪剂研究和新型肝和代谢成像进行培训。这项受过指导的研究经验将促进她成为成功的独立医师科学家的发展。公共卫生相关性：这项研究将提高人们对果糖在小儿非酒精性脂肪肝疾病中的作用的了解，这种疾病影响了美国超过300万儿童。这些研究旨在改善儿童治疗和预防NAFLD的治疗，从而改善数百万儿童的健康。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Update in childhood and adolescent obesity.

儿童和青少年肥胖的最新进展。

DOI：
10.1016/j.pcl.2011.09.016
发表时间：
2011
期刊：
Pediatric clinics of North America
影响因子：
2.6
作者：
Vos,Miriam;Barlow,SarahE
通讯作者：
Barlow,SarahE

Consumption of added sugars and indicators of cardiovascular disease risk among US adolescents.

DOI：
10.1161/circulationaha.110.972166
发表时间：
2011-01-25
期刊：
Circulation
影响因子：
37.8
作者：
Welsh JA;Sharma A;Cunningham SA;Vos MB
通讯作者：
Vos MB

Plasminogen Activator Inhibitor-1 Predicts Quantity of Hepatic Steatosis Independent of Insulin Resistance and Body Weight.

DOI：
10.1097/mpg.0000000000001096
发表时间：
2016-06
期刊：
Journal of pediatric gastroenterology and nutrition
影响因子：
2.9
作者：
Holzberg JR;Jin R;Le NA;Ziegler TR;Brunt EM;McClain CJ;Konomi JV;Arteel GE;Vos MB
通讯作者：
Vos MB

Childhood obesity: update on predisposing factors and prevention strategies.