Toxic AGE (TAGE) Theory for the Pathophysiology of the Onset/Progression of NAFLD and ALD.
Toxic AGE (TAGE) Theory for the Pathophysiology of the Onset/Progression of NAFLD and ALD.
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DOI：
10.3390/nu9060634
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发表时间：
2017-06-20
期刊：
影响因子：
5.9
通讯作者：
Tsutsumi M
中科院分区：
文献类型：
--
作者：
Takeuchi M;Takino JI;Sakasai-Sakai A;Takata T;Tsutsumi M
非酒精性脂肪肝病（NAFLD）和酒精性肝病（ALD）是西方世界慢性肝病的最常见原因之一。 NAFLD和ALD经常伴有肝外并发症，包括肝细胞癌和心血管疾病，这对患者的生存产生负面影响。长期摄入过量含糖/高果糖玉米糖浆的日常饮食会增加果糖/葡萄糖代谢物甘油醛（GA）的水平，而长期饮用过量酒精饮料会增加肝脏中酒精代谢物乙醛（AA）的水平。已知 GA 和 AA 与蛋白质的 ε- 或 α- 氨基发生非酶促反应，从而在体内产生高级糖基化终产物（分别为 AGE、GA-AGE 和 AA-AGE）。 GA-AGEs 和 AGEs 受体 (RAGE) 之间的相互作用改变细胞内信号传导、基因表达和促炎分子的释放，还引起人肝细胞和肝星状细胞产生活性氧，所有这些都可能导致与慢性肝病相关的病理变化。我们在此讨论 GA-AGE 和 AA-AGE（有毒 AGE，TAGE）的病理生理学作用以及预防 NAFLD 和 ALD 发病/进展的相关新理论。
Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are among the most common causes of chronic liver diseases in the westernized world. NAFLD and ALD are frequently accompanied by extrahepatic complications, including hepatocellular carcinoma and cardiovascular diseases, which have a negative impact on patient survival. The chronic ingestion of an excessive daily diet containing sugar/high-fructose corn syrup increases the level of the fructose/glucose metabolite, glyceraldehyde (GA), while the chronic consumption of an excessive number of alcoholic beverages increases the level of the alcohol metabolite, acetaldehyde (AA) in the liver. GA and AA are known to react non-enzymatically with the ε- or α-amino groups of proteins, thereby generating advanced glycation end-products (AGEs, GA-AGEs, and AA-AGEs, respectively) in vivo. The interaction between GA-AGEs and the receptor for AGEs (RAGE) alters intracellular signaling, gene expression, and the release of pro-inflammatory molecules and also elicits the production of reactive oxygen species by human hepatocytes and hepatic stellate cells, all of which may contribute to the pathological changes associated with chronic liver diseases. We herein discuss the pathophysiological roles of GA-AGEs and AA-AGEs (toxic AGEs, TAGE) and a related novel theory for preventing the onset/progression of NAFLD and ALD.