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. 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, ALT, AST, fasting glucose, fasting insulin, insulin resistance and glucose tolerance were assessed. Histology revealed that neutrophil infiltration occurred in the livers of the high AGE group at week 26; steatosis was not found with the inflamed livers. At week 39 livers from both groups exhibited 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 ALT (P<0.01) and AST (P=0.02) than those of the high AGE group. We demonstrate that a high AGE diet can cause liver inflammation in the absence of steatosis. Our results are the first to show that dietary AGE can contribute to the pathogenesis of NASH.