title: Expression of perilipin and adipophilin in nonalcoholic fatty liver disease; relevance to oxidative injury and hepatocyte ballooning.
abstract: OBJECTIVE
  Perilipin and adipophilin, PAT family proteins, play important roles in lipid metabolism. Although nonalcoholic fatty liver disease (NAFLD) is initiated by hepatocyte lipidation, little is known about the relationship between these proteins and hepatocellular injury. We investigated the expressions of perilipin and adipophilin and their relation to inflammation, fibrosis, hepatocellular ballooning, and oxidized phosphatidylcholine (oxPC) localization in human NAFLD.
  
  
  RESULTS
  Liver biopsies of nonalcoholic steatohepatitis (NASH, n=39) or simple steatosis (n=9) were studied by immunohistochemical techniques using anti-perilipin, anti-adipophilin and anti-oxPC antibodies. The severity of liver damage was histologically assessed by the Brunt system and NAFLD activity score (NAS). Enlarged hepatocytes usually containing Mallory-Denk bodies were defined as ballooned. Perilipin and adipophilin were detected on the rim of lipid droplets in both NASH and simple steatosis. Perilipin was more evident in larger lipid droplets while adipophilin expression was frequent in lipid droplets of ballooned hepatocytes. The frequency of adipophilin-positive ballooned hepatocytes was correlated to inflammation (Rs=0.72, p<0.0001), fibrosis (Rs=0.46, p=0.005), NAS (Rs=0.47, p=0.004) and oxPC-positive ballooned hepatocytes (Rs=0.35, p=0.033).
  
  
  CONCLUSIONS
  Expression patterns of perilipin and adipophilin in NASH livers varied with the size of lipid droplets. In partiew or, adipophilin expression in ballooned hepatocytes was closely associated with oxidative damage.
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ikura
authors.forename: Junko
authors.initials: J
authors.lastname: Arimoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugioka
authors.forename: Julia C
authors.initials: JC
authors.lastname: Iezzoni
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Takahiko
authors.initials: T
authors.lastname: Naruko
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Itabe
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Caldwell
authors.forename: Makiko
authors.initials: M
authors.lastname: Ueda
mesh_terms: D000328:Adult; D001706:Biopsy; D002352:Carrier Proteins; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D018384:Oxidative Stress; D010455:Peptides / Q000378:metabolism*; D000070778:Perilipin-1; D000070780:Perilipin-2; D010713:Phosphatidylcholines / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis*
chemical_list: D002352:Carrier Proteins; D008055:Lipids; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D010455:Peptides; D000070778:Perilipin-1; D000070780:Perilipin-2; D010713:Phosphatidylcholines; D010750:Phosphoproteins