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.
PLoS One. 2012;7(4):e35143. doi: 10.1371/journal.pone.0035143. Epub 2012 Apr 4.
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, alanine aminotransferase, aspartate aminotransferase, 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 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.
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.
研究饮食中的晚期糖基化终产物（AGEs）对肝脏健康的影响及其在非酒精性脂肪性肝炎（NASH）发病机制中的可能作用。
两组小鼠喂养相同的饮食，除了 AGE 含量不同。一组喂养高 AGE 饮食，另一组喂养常规 AGE 饮食。评估肝组织学、丙氨酸转氨酶、天冬氨酸转氨酶、空腹血糖、空腹胰岛素、胰岛素抵抗和葡萄糖耐量。
组织学显示，高 AGE 组的肝脏在第 26 周发生中性粒细胞浸润；脂肪变性不伴有肝炎症。在第 39 周，两组的肝脏均表现出大或小脂肪变性，但未检测到炎症。与高 AGE 组相比，常规 AGE 组在第 26 周（P = 0.034）检测到更高的胰岛素水平。在第 39 周，常规 AGE 组的丙氨酸转氨酶（P<0.01）和天冬氨酸转氨酶（P = 0.02）水平均高于高 AGE 组。
我们证明高 AGE 饮食可在无脂肪变性的情况下引起肝炎症。我们的结果表明，饮食中的 AGE 可能在启动肝炎症中发挥作用，从而促进 NASH 的疾病进展。我们观察到高 AGE 单独引起的炎症不会持续存在，这表明未来有有趣的研究方向，可以研究 AGE 如何在肝脏中参与促氧化和抗氧化途径。
