title: Effect of dietary advanced glycation end products on mouse liver.
abstract: The exact pathophysiology of non-alcoholic steatohepatitis (NASH) is not known. Previous studies suggest that dietary advanced glycation end products (AGEs) can cause oxidative stress in liver. We aim to study the effects of dietary AGEs on liver health and their possible role in the pathogenesis of NASH.
  
  
  METHODS
  Two groups of mice were fed the same diet except the AGE content varied. One group was fed a high AGE diet and the second group was fed a regular AGE diet. Liver histology, alanine aminotransferase, aspartate aminotransferase, fasting glucose, fasting insulin, insulin resistance and glucose tolerance were assessed.
  
  
  RESULTS
  Histology revealed that neutrophil infiltration occurred in the livers of the high AGE group at week 26; steatosis did not accompany liver inflammation. At week 39 livers from both groups exhibited macro- or micro-steatosis, yet no inflammation was detected. Higher insulin levels were detected in the regular AGE group at week 26 (P = 0.034), compared to the high AGE group. At week 39, the regular AGE group showed higher levels of alanine aminotransferase (P<0.01) and aspartate aminotransferase (P = 0.02) than those of the high AGE group.
  
  
  CONCLUSIONS
  We demonstrate that a high AGE diet can cause liver inflammation in the absence of steatosis. Our results show that dietary AGEs could play a role in initiating liver inflammation contributing to the disease progression of NASH. Our observation that the inflammation caused by high AGE alone did not persist suggests interesting future directions to investigate how AGEs contribute to pro-oxidative and anti-oxidative pathways in the liver.
authors.affiliation: Department of Pediatrics, Digestive Diseases and Nutrition Center, State University of New York, Women and Children's Hospital of Buffalo, Buffalo, New York, United States of America.
authors.forename: Raza
authors.initials: R
authors.lastname: Patel
authors.forename: Susan S
authors.initials: SS
authors.lastname: Baker
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.forename: Sonal
authors.initials: S
authors.lastname: Desai
authors.forename: Razan
authors.initials: R
authors.lastname: Alkhouri
authors.forename: Rafal
authors.initials: R
authors.lastname: Kozielski
authors.forename: Lucy
authors.initials: L
authors.lastname: Mastrandrea
authors.forename: Adil
authors.initials: A
authors.lastname: Sarfraz
authors.forename: Weijing
authors.initials: W
authors.lastname: Cai
authors.forename: Helen
authors.initials: H
authors.lastname: Vlassara
authors.forename: Mulchand S
authors.initials: MS
authors.lastname: Patel
authors.forename: Robert D
authors.initials: RD
authors.lastname: Baker
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D004032:Diet / Q000009:adverse effects*; D005215:Fasting / Q000097:blood; D005234:Fatty Liver / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D005951:Glucose Tolerance Test; D017127:Glycation End Products, Advanced / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects
chemical_list: D017127:Glycation End Products, Advanced; D007328:Insulin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase