studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 671A
938
Alterations in NK cell phenotype with disease progression
in a murine model of non-alcoholic fatty liver disease
(NAFLD)
Rachel McMahan, Cara Porsche, Lucy Golden-Mason, Hugo R.
Rosen; Gastroenterology, University of Colorado, Aurora, CO
Background: Nonalcoholic fatty liver disease (NAFLD) is associated
with a spectrum ranging from benign accumulation of triglycerides
within the cytoplasm of liver hepatocytes (steatosis)
to a more severe disease, nonalcoholic steatohepatitis (NASH).
While the function of NKT cells in NAFLD progression has been
extensively investigated, there are limited data on the role of
NK cells in this disease. To further clarify the role of these cells
in NAFLD we analyzed NK cell phenotype and function over
time in a murine model of NAFLD. Methods: To investigate the
role of NK cells during NAFLD disease progression we established
a murine model of NAFLD/NASH demonstrating the full
disease spectrum. Mice were fed high fat, high cholesterol, high
sucrose diet containing trans-fats from 8 weeks to 20 weeks.
NAFLD severity at 8, 12 and 20 weeks was evaluated by
liver histology and intrahepatic gene expression. NK cells were
isolated from livers at the indicated time points and stained
for cell surface markers and degranulation. Results: We have
established a murine progressive NAFLD model mimicking the
disease spectrum observed in NASH/NAFLD. After 8 weeks of
feeding the mice had increased hepatic steatosis without significant
inflammation while at the 12 week time point inflammatory
foci were found along with increased macrovesicular steatosis.
By 20 weeks, the mice had also developed significant fibrosis
along with inflammation and steatosis mimicking NASH. As
disease progressed from steatosis to steatohepatitis intrahepatic
NK cells significantly increased expression of activation
markers (CD69, p