Page 96 - ebook HCC

PROGRAMME
94
94 PROGRAMME AND ABSTRACTSAND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 95
FEBRUARY 13 - 16, 2014

Poster Board Number B4

SEQUENTIAL EXPRESSION OF LIPID NOTES
DROPLET-ASSOCIATED PROTEINS OF THE
PERILIPIN FAMILY DURING STEATOGENESIS:
IMPLICATIONS FOR STEATOHEPATITIS AND
MALIGNANT PROGRESSION

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Beate K. Straub , Lena Pawella , Merita Hashani , Peter Schirmacher 1
1 Institute of Pathology, University Clinic Heidelberg, 69120 Heidelberg, Germany
Corresponding author’s e-mail: beate.straub@med.uni-heidelberg.de
Introduction: Hepatocellular steatosis is the most frequent liver disease in the western
world and may develop further to steatohepatitis, liver cirrhosis, and hepatocellular
carcinoma. We have previously shown that lipid droplet (LD)-associated proteins of the
perilipin family (perilipin 1-5) are differentially expressed in hepatocyte steatosis and
hepatocellular carcinoma (HCC) and that perilipin 1 is de novo expressed in chronic
steatosis, but only found in a minority of HCCs.

Aims: Aim of this study was to analyse perilipin expression in bland steatosis versus
BASIC POSTER ABSTRACTS Methodology: In vitro, steatosis models were combined with stable downregulation of BASIC POSTER ABSTRACTS
steatohepatitis and HCCas well as in cell culture models in order to explore the diagnostic
and therapeutic potential of perilipins.
perilipin 2 and/or perilipin 3 and hypoxic as well as lipolytic conditions. In parallel, immuno-
histochemical analyses of perilipins were performed with over 100 liver biopsies with
steatosis, steatohepatitis and HCC.

Results: In short-term steatosis models in vitro, perilipins 3 and 5 were recruited to LDs
and in chronic steatosis, perilipin 3 and 5 were gradually replaced by perilipin 2 and finally
perilipin 1 at LDs of increasing size. In this line, in acute/toxic microvesicular steatosis
in situ, perilipins 2, 3 and 5 were detected at LDs, but perilipin 1 was virtually absent;
by contrast, perilipins 1 and 2-positive LDs were strongly increased in human chronic
macrovesicular liver disease irrespective of the underlying etiology, whereas perilipins 3
and 5 were localized cytoplasmically and not at LDs. In steatohepatitis, ballooned cells
were characterized by coexpression of perilipin 2, 3 and 5, but not perilipin 1. Also in HCC,
perilipin 2, 3 and 5, but not perilipin 1 were frequently upregulated. In steatosis models
under stable downregulation of perilipin 2 and/or 3, perilipin 1 was increased with reduced
LD number and increased LD size. Interestingly, cell vitality in cells lacking perilipin 2
and/or 3 was decreased, especially under conditions of stress as e.g. hypoxia. Under
conditions of lipolysis, perilipin 1 phophorylation controlled LD breakdown.
Conclusions: LD-maturation in hepatocytes in vivo and in vitro involves sequential
perilipin expression. Ballooned cells in steatohepatitis and hepatocellular carcinoma cells
overexpress small, newly formed LDs. Due to their central position in LD-biogenesis,
structure and break-down, perilipins may be interesting diagnostic and therapeutic targets
in steatotic liver disease.