The Role of Lipin-1 in the Pathogenesis of Alcoholic Fatty Liver
The Role of Lipin-1 in the Pathogenesis of Alcoholic Fatty Liver
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DOI：
10.1093/alcalc/agu102
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发表时间：
2015-03-01
影响因子：
2.8
通讯作者：
Zhou, Junying
中科院分区：
文献类型：
--
作者：
Bi, Lijuan;Jiang, Zhian;Zhou, Junying
目的：本综述的目的是关注脂素-1在酒精性脂肪肝发病机制中的作用。方法：系统回顾脂素-1在酒精性脂肪肝、酒精性肝炎和酒精性肝硬化中的作用的动物临床和细胞水平研究。结果：乙醇可通过AMPK-SREBP-1信号通路增加lipin-1的表达，并通过SIRT1-SFRS10-Lpin1 β / α轴显著增加肝脏中Lpin1 β与Lpin1 α的比值。此外，研究表明，过表达lipin-1也能显著抑制极低密度脂蛋白-甘油三酯的分泌。最后，脂素-1具有有效的抗炎特性。结论：脂质-1在脂质代谢中具有双重功能。在细胞质中，脂素-1 β在甘油三酯合成途径中作为Mg2+依赖性磷脂酸磷酸水解酶（PAP）酶发挥作用。在细胞核中，脂素-1 α作为转录共调节剂调节肝脏脂肪酸氧化能力和脂肪生成酶的活性。在酒精性脂肪性肝病（AFLD）肝细胞中，乙醇通过AMPK-SREBP-1信号通路和SIRT1-SFRS10- Lpin1 β / α轴增加lipin-1的表达和Lpin1 β / α比值。当然，除此之外，乙醇也可以产生PAP活性，中断脂素-1的细胞核功能。此外，过表达脂素-1可以显著抑制极低密度脂蛋白三酰甘油（VLDL-TAG）的分泌。最后，内源性脂素-1具有有效的抗炎特性。TAG合成增加，脂肪酸氧化减少，VLDL-TAG分泌受损，炎症因子激活，共同作用加剧AFLD的发展。
Aims: The aim of this review was to focus on the knowledge of the role of lipin-1 in the pathogenesis of alcoholic fatty liver. Methods: Systematic review of animal clinical and cell level studies related to the function of lipin-1 on alcoholic fatty liver, alcoholic hepatitis and alcoholic liver cirrhosis disease. Result: Ethanol could increase the expression of lipin-1 through the AMPK-SREBP-1 signaling and dramatically increase the ratio of Lpin1 beta to Lpin1 alpha by SIRT1-SFRS10-Lpin1 beta/alpha axis in the liver. Moreover, research has shown that over-expression of lipin-1 could also remarkably suppress very low density lipoprotein-triacylglyceride secretion. Last, lipin-1 has potent anti-inflammatory property. Conclusion: In conclusion, lipin-1 has dual functions in lipid metabolism. In the cytoplasm, lipin-1 beta functions as a Mg2+-dependent phosphatidic acid phosphohydrolase (PAP) enzyme in triglyceride synthesis pathways. In the nucleus, lipin-1 alpha acts as a transcriptional co-regulator to regulate the capacity of the liver for fatty acid oxidation and activity of the lipogenic enzyme. In hepatocytes of alcoholic fatty liver disease (AFLD), ethanol increases the expression of lipin-1 through the AMPK-SREBP-1 signaling and the Lpin1 beta/alpha ratio by SIRT1-SFRS10- Lpin1 beta/alpha axis. Of course, in addition to that, ethanol could also produce the PAP activity and interrupt the nucleus function of lipin-1. Furthermore, over-expression of lipin-1 could remarkably suppress very low-density lipoprotein-triacylglyceride (VLDL-TAG) secretion. In the end, endogenous lipin-1 has potent anti-inflammatory property. Increased synthesis of TAG, decreased fatty acid oxidation, impaired VLDL-TAG secretion and activated inflammatory factors act together to exacerbate the development of AFLD.