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.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver enzymes in the U.S [1], accounting for a quarter of all chronic liver diseases [2]
Our results show that dietary advanced glycation end products (AGEs) can cause liver inflammation and contribute to the pathogenesis of nonalcoholic steatohepatitis (NASH)
Inflammatory foci were detected in mouse livers at week 26 when fed with a high AGE diet, while mice fed the regular AGE diet remained free from liver inflammation throughout the length of the 39 week study
Summary
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver enzymes in the U.S [1], accounting for a quarter of all chronic liver diseases [2]. NAFLD occurs in approximately 40– 90% of all obese individuals and 15% of those individuals progress to NAFLD’s severe form, NASH [3,4,5]. Evidence from animal models and human studies suggests that oxidative stress is one of the key factors in the disease progression of NASH [7,8,9]. One pathway is related to impaired electron flow through the mitochondrial respiratory chain (MRC) [10,11]. MRC impairment increases fatty acid oxidation at peroxisomes and endoplasmic reticulum, resulting in the production of additional reactive oxygen species (ROS) [13,14]. An animal model [15] and a human study [16] suggest that alcohol produced by obesity-related colonic microbes can contribute to the elevated ROS production
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