高尔基体跨膜糖蛋白73高表达诱发脂肪肝的脂类特性分析

Lipid characteristics of fatty liver induced by high expression of Golgi protein 73

摘要:

脂肪性肝病是最常见的慢性肝脏疾病，脂质代谢异常是脂肪性肝病发生的重要原因。为研究高尔基体糖蛋白（Golgi protein 73，GP73）对肝脏脂质代谢的影响，选用八周龄C57BL/6J小鼠通过尾静脉注射搭载GP73的腺相关病毒（AAV-GP73），构建肝脏特异性高表达GP73的小鼠，通过对肝脏进行脂质代谢组学分析发现小鼠肝脏中的脂质尤其是甘油三酯明显增加。京都基因与基因组百科全书（kyoto encyclopedia of genes and genomes，KEGG）富集分析显示，GP73通过引起脂代谢产物的改变导致诸多与细胞代谢活动相关的信号通路出现紊乱，特别是与人类密切相关的疾病如Ⅱ型糖尿病、非酒精性脂肪性肝病（NAFLD）和癌细胞胆碱代谢更可能发生失调。研究表明，GP73可能通过参与调控脂类代谢并促进肝脏内脂质积累诱发脂肪肝。

Abstract:

Fatty liver disease is a common chronic liver disease which is mainly induced by abnormal lipid metabolism. To find out the effect of GP73 on lipid metabolism in the liver, we constructed a high GP73 expression liver model through a tail vein injection of AAV-GP73 into eight-week-old C57BL/6J mice. Liver lipid metabolomics analysis showed that lipids in the liver of mice, especially the triglycerides, were significantly increased. In addition, kyoto encyclopedia of genes and genomes enrichment analysis showed that GP73 altered lipid metabolites profile that may further disturb many signaling pathways related to cellular metabolism. The diseases linked to type II diabetes, non-alcoholic fatty liver disease (NAFLD) and choline metabolism in cancer cells were more likely to be dysregulated. Thus, GP73 may induce fatty liver by regulating lipid metabolism and promoting lipid accumulation in the liver.