title: The role of lipin-1 in the pathogenesis of alcoholic fatty liver.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  Ethanol could increase the expression of lipin-1 through the AMPK-SREBP-1 signaling and dramatically increase the ratio of Lpin1β to Lpin1α by SIRT1-SFRS10-Lpin1β/α 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.
  
  
  CONCLUSIONS
  In conclusion, lipin-1 has dual functions in lipid metabolism. In the cytoplasm, lipin-1β functions as a Mg(2+)-dependent phosphatidic acid phosphohydrolase (PAP) enzyme in triglyceride synthesis pathways. In the nucleus, lipin-1α 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 Lpin1β/α ratio by SIRT1-SFRS10- Lpin1β/α 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.
authors.affiliation: Department of Infectious Disease, Third Hospital, Hebei Medical University, 139 ZiQiang Road, Shijiazhuang 050051, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Bi
authors.affiliation: Department of Infectious Disease, Third Hospital, Hebei Medical University, 139 ZiQiang Road, Shijiazhuang 050051, China.
authors.forename: Zhian
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Infectious Disease, Third Hospital, Hebei Medical University, 139 ZiQiang Road, Shijiazhuang 050051, China doctorzhoujy@163.com.
authors.forename: Junying
authors.initials: J
authors.lastname: Zhou
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D005235:Fatty Liver, Alcoholic / Q000378:metabolism*; D006519:Hepatitis, Alcoholic / Q000378:metabolism*; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D010711:Phosphatidate Phosphatase / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D051780:Sterol Regulatory Element Binding Protein 1; C100345:Tra2b protein, mouse; D014280:Triglycerides; D000068103:Serine-Arginine Splicing Factors; D055372:AMP-Activated Protein Kinases; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase; D056564:Sirtuin 1