The Role of Lipin-1 in the Pathogenesis of Alcoholic Fatty Liver

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.