Novel pathway for iron deficiency in pediatric non‐alcoholic steatohepatitis (1042.1)

Abstract

Non‐alcoholic steatohepatitis (NASH) is an obesity related liver disease characterized by steatosis and inflammation. Iron may play a role in NASH pathology as it catalyzes the production of reactive oxygen species. To examine the iron status in pediatric NASH, serum iron, ferritin, and soluble transferrin receptor 1 in NASH patients were compared to those in the National Health and Nutrition Examination Survey database. Serum iron and soluble transferrin receptor 1 were decreased while serum ferritin was increased in NASH patients. No detectable iron was observed in NASH liver by Perls’ Prussian blue staining. Microarray and quantitative real‐time PCR indicated that the mRNA of transferrin, transferrin receptor 2 and catalase were significantly elevated in NASH patients, and that transferrin mRNA was positively correlated with catalase mRNA. To test the hypothesis that oxidative stress induces iron deficiency, HepG2 cells were treated with H2O2, and the mRNA of transferrin and catalase were induced and positively correlated. We conclude that there is a tendency towards iron deficiency in pediatric NASH patients. Increased liver gene expression of transferrin and transferrin receptor 2 supports a status of iron deficiency. Our finding that H2O2 induces the expression of transferrin, and consequently, decreased iron absorption, suggests a novel mechanism for iron deficiency in NASH patients.