ISOPROSTANES: A MARKER OF OXIDATIVE INJURY IN NON-ALCOHOLIC FATTY LIVER DISEASE

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Childhood obesity is a burgeoning epidemic in the United States. Accompanying this rise in obesity, is a rise in non-alcoholic fatty liver disease. Estimates indicate that NAFLD affects up to 1.6 million American children. A subgroup of these children have non-alcoholic steatohepatitis (NASH), an aggressive necro-inflammatory disease that may lead to fibrosis and cirrhosis. Oxidative injury is thought to be a key component in the progression from benign steatosis to NASH. A thorough understanding of oxidant injury in vivo has previously been difficult because of a lack of reliable and noninvasive indexes of oxidant stress. In recent years, measurements of isoprostanes have shown promise. The injury initiated by oxidative stress may be propagated by cytokines. Aims: 1) To establish the utility of plasma and urinary isoprostanes as markers of oxidative injury pediatric NAFLD/NASH. 2) To explore the relationship of oxidative injury, as measured by plasma and urinary isoprostanes and pro-inflammatory and anti-inflammatory cytokines in pediatric NAFLD/NASH. Methods: Three patient populations, ages 10 to 18, will be studied: 1) overweight subjects known to have NAFLD/NASH, 2) overweight subjects without evidence of liver disease and 3) healthy weight controls without liver disease. Overweight will be defined as body mass index (BMI) BMI greater than 95%ile for age. Studies including a physical exam, anthropometrics, demographics, ALT/AST, fasting insulin, glucose and lipid profile, serum leptin and cytokines will be performed. Additionally, urinary and serum isoprostanes will be analyzed. Some patients will receive an abdominal ultrasound. Analysis: Appropriate statistical analysis will be performed to understand the utility of isoprostanes in the study of pediatric NAFLD/NASH.