Dietary Fructose and Redox Effects in Pediatric Nonalcoholic Fatty Liver Disease

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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.