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DOI: 10.1055/s-2008-1037541
Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis
Introduction: Fatty change (steatosis) is the most frequent liver pathology in western countries and is caused by a broad range of disorders such as alcohol abuse and metabolic syndrome. The surface layer of lipid droplets (LDs) contains members of a protein family that share homologous sequences and domains, the so-called PAT proteins, named after their constituents, perilipin, adipophilin, and TIP47.
Material& Methods: The expression of PAT proteins in liver specimens of different species was analysed using immunohistochemical, protein biochemical as well as molecular biological methods.
Results: We characterized the LD-associated proteins in normal and diseased liver connected with LD accumulation. Adipophilin and TIP47 are expressed in LDs of vitamin A storing hepatic stellate cells and additionally in LDs of steatotic hepatocytes. Perilipin, which was thought to be characteristic for LDs of adipocytes and steroidogenic cells, becomes de novo expressed in hepatocytes of human steatotic liver. Perilipin splice variant A was found to be present in human steatotic hepatocytes by biochemical, molecular biological and immunohistochemical methods. Its association with LDs is different from TIP47 and adipophilin, with respect to size and localization of the LDs, suggesting that the different PAT proteins play specific roles during maturation of LDs. Both the amounts of adipophilin and perilipin splice variant A positively correlated with the amount of hepatocytic fat.
Conclusion: We recommend that the expression of perilipin can be used as a new diagnostic marker for human fatty liver disease and that perilipin may represent a potential target for the suppression of hepatic steatosis.
PAT proteins - fatty liver disease - perilipin