More than 20% of children in the United States are overweight and almost one fourth of these have obesity related fatty liver disease (NAFLD). This condition can progress to cirrhosis over time and leads to significant morbidity and mortality in adulthood. Currently, there is not an effective prevention or treatment for pediatric NAFLD. Most theories of pathogenesis involve oxidative stress leading to upregulation of cytokines as a key factor. Better understanding of the role of cytokines and oxidative stress in pediatric NAFLD would allow future improvements in the prevention, identification and therapy of this disease. Preliminary work suggests that levels of cytokines and oxidative stress will correlate with the presence of NAFLD in children, and that this dysregulation of the immune system will improve when treated with an effective antioxidant. Therefore, the specific objectives are 1.) To correlate baseline serum cytokines and cytokine response of immune cells (priming) with indices of pediatric NAFLD; 2.) To evaluate intracellular levels of antioxidants Sadenosylmethionine (SAMe) and glutathione as well as transcription factors AP-1 and NFkappaB and correlate these with NAFLD, 3.) To determine if SAMe supplementation can decrease immune cell priming and decrease oxidative stress, initially in an ex vivo system and in a subsequent pilot treatment study.
| Vos, Miriam B; Weber, Mary Beth; Welsh, Jean et al. (2009) Fructose and oxidized low-density lipoprotein in pediatric nonalcoholic fatty liver disease: a pilot study. Arch Pediatr Adolesc Med 163:674-5 |
