title: Novel pathway for iron deficiency in pediatric non-alcoholic steatohepatitis.
abstract: OBJECTIVE
  Iron may be an important factor in the pathogenesis of non-alcoholic steatohepatitis (NASH) as it catalyzes the production of potent reactive oxygen species. We aim to examine iron status in pediatric NASH.
  
  
  METHODS
  Serum indices of NASH patients (N = 36) were compared to those in the U.S. National Health and Nutrition Examination Survey database (N = 802). Iron related gene expression was examined in NASH livers and normal livers, using microarray and quantitative real-time PCR (10 NASH livers and 6 controls). Transferrin and catalase expression were also examined in hydrogen peroxide treated HepG2 cells.
  
  
  RESULTS
  Serum iron concentration (P < 0.01) and soluble transferrin receptor 1 (P < 0.0001) were decreased while serum ferritin was elevated in NASH patients (P < 0.01). No detectable iron was observed in NASH liver by Perls' Prussian blue staining. Transferrin (P < 0.01) and transferrin receptor 2 (P < 0.01) mRNA were elevated in NASH patients. Of particular interest, transferrin mRNA was positively correlated with catalase mRNA (r = 0.9338, P < 0.0001). H2O2 treatment of HepG2 cells induced mRNA expression of transferrin and catalase.
  
  
  CONCLUSIONS
  Pediatric NASH patients exhibited decreased serum iron concentration and no detectable iron was observed in any NASH liver by Perls' Prussian blue staining. These changes are consistent with the facts that most NASH patients are obese and exhibit chronic inflammation. In line with a status of iron deficiency, gene expression studies suggested decreased expression of transferrin and transferrin receptor 2 in NASH livers. Induction of transferrin by H2O2, and consequently, decreased iron absorption, suggests a novel mechanism for iron deficiency in NASH patients.
authors.affiliation: Department of Pediatrics, SUNY at Buffalo, United States; Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, United States.
authors.forename: Diana
authors.initials: D
authors.lastname: Moya
authors.affiliation: Department of Pediatrics, SUNY at Buffalo, United States; Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, United States. Electronic address: sbaker@upa.chob.edu.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Baker
authors.affiliation: Department of Pediatrics, SUNY at Buffalo, United States; Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, United States.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, SUNY at Buffalo, United States; Department of Biochemistry, SUNY at Buffalo, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Garrick
authors.affiliation: Department of Pathology, SUNY at Buffalo, Women and Children's Hospital of Buffalo, Buffalo, NY 14214, United States.
authors.forename: Rafal
authors.initials: R
authors.lastname: Kozielski
authors.affiliation: Department of Pediatrics, SUNY at Buffalo, United States; Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, United States.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Baker
authors.affiliation: Department of Pediatrics, SUNY at Buffalo, United States; Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, United States. Electronic address: lixinzhu@buffalo.edu.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D018798:Anemia, Iron-Deficiency / Q000097:blood* / Q000209:etiology; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005293:Ferritins / Q000097:blood; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000150:complications; D009749:Nutrition Surveys; D009752:Nutritional Status; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*; D014168:Transferrin / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D014168:Transferrin; D005293:Ferritins; D006861:Hydrogen Peroxide; D007501:Iron
keywords: Catalase; Hydrogen peroxide; NHANES; Transferrin; Transferrin receptor 2