Lipid droplet-associated proteins in steatosis. Effects of induction and siRNA-mediated downregulation of PAT proteins in cell culture models of hepatocyte steatosis

Background. The accumulation of hepatocellular lipid droplets, referred to as steatosis, is the most frequent liver pathology in western industrial countries. The surface of lipid droplets is stabilized by amphiphilic proteins of the PAT family (perilipin, adipophilin, TIP47). We recently showed that PAT proteins are differentially expressed in liver. Methods. The effects of lipid droplet induction with oleate and of siRNA-mediated downregulation of PAT proteins were evaluated using immunofluorescence microscopy, immunoblot and functional assays. Results. Whereas perilipin, adipophilin and (in only minor amounts) also TIP47 coat lipid droplets in steatotic hepatocytes, adipophilin and TIP47, but not perilipin, are detectable in hepatocellular cell cultures. Likewise, perilipin is not induced after downregulation of adipophilin and TIP47. Conclusions. Common cell culture models show specific differences to human hepatocyte steatosis in vivo. Perilipin may play a role in the long-term storage of fat, which may be only partially reflected by cell culture models.