Expression of perilipin and adipophilin in nonalcoholic fatty liver disease; relevance to oxidative injury and hepatocyte ballooning.
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.
Fujii
Hideki
H
Department of Hepatology, Osaka City University Graduate School of Medicine, Japan.
Ikura
Yoshihiro
Y
Arimoto
Junko
J
Sugioka
Kenichi
K
Iezzoni
Julia C
JC
Park
Sang Hoon
SH
Naruko
Takahiko
T
Itabe
Hiroyuki
H
Kawada
Norifumi
N
Caldwell
Stephen H
SH
Ueda
Makiko
M
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*
D002352:Carrier Proteins; D008055:Lipids; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D010455:Peptides; D000070778:Perilipin-1; D000070780:Perilipin-2; D010713:Phosphatidylcholines; D010750:Phosphoproteins