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Int J Clin Exp Pathol 2010;3(5):505-514

Original Article
Expression of fatty acid synthase in nonalcoholic fatty liver disease

Christoph Dorn, Marc-Oliver Riener, Georgi Kirovski, Michael Saugspier, Kathrin Steib, Thomas S. Weiss, Erwin Gäbele, Glen Kristiansen,
Arndt Hartmann, Claus Hellerbrand

Department of Internal Medicine I, University Hospital Regensburg, Germany; Institute of Pathology, University Hospital Erlangen, Germany;
Department of Surgery, University Hospital Regensburg, Germany; Department of Pathology, University Hospital Zurich, Switzerland.

Received May 14, 2010, accepted May 21, 2010, available online: March 25, 2010

Abstract: Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation which starts with simple hepatic steatosis
and may progress toward inflammation (nonalcoholic steatohepatitis [NASH]). Fatty acid synthase (FASN) catalyzes the last step in fatty acid
biosynthesis, and thus, it is believed to be a major determinant of the maximal hepatic capacity to generate fatty acids by de novo lipogenesis.
The aim of this study was to analyze the correlation between hepatic steatosis and inflammation with FASN expression. In vitro incubation of
primary human hepatocytes with fatty acids dose-dependently induced cellular fatty acidaccumulation and FASN expression, while stimulation
with TNF did not affect FASN levels. Further, hepatic FASN expression was significantly increased in vivo in a murine model of hepatic steatosis
without significant inflammation but not in a murine NASH model as compared to control mice. Also, FASN expression was not increased
in mice subjected to bile duct ligation, an experimental model characterized by severe hepatocellular damage and inflammation. Furthermore,
FASN expression was analyzed in 102 human control or NAFLD livers applying tissue micro array technology and immunohistochemistry, and
correlated significantly with the degree of hepatic steatosis, but not with inflammation or ballooning of hepatocytes. Quantification of FASN
mRNA expression in human liver samples confirmed significantly higher FASN levels in hepatic steatosis but not in NASH, and expression of
SREBP1, which is the main transcriptional regulator of FASN, paralleled FASN expression levels in human and experimental NAFLD. In
conclusion, the transcriptional induction of FASN expression in hepatic steatosis is impaired in NASH, while hepatic inflammation in the
absence of steatosis does not affect FASN expression, suggesting that FASN may serve as a new diagnostic marker or therapeutic target for
the progression of NAFLD. (IJCEP1005005).

Key words: FASN, NAFLD, NASH, SREBP1

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Address all correspondence to:
Claus Hellerbrand, MD
University Hospital Regensburg
Department of Internal Medicine I
D-93042 Regensburg
Germany
Tel: +49-941-944-7155
Fax: +49-941-944-7154
E-mail:
claus.hellerbrand@klinik.uni-regensburg.de