At least one quarter of individuals with chronic hepatitis B virus (HBV) infection
have fatty livers, but little is known about the influence of HBV on hepatic steatosis.
Furthermore, hepatic steatosis is a known risk factor for disease progression in HBV-infected
individuals but the underlying mechanisms are widely unknown.
The aim of this study was to establish a model to study the effect of HBV on hepatic steatosis and lipotoxicity.
Methods and Results: The HBV producing cell lines HepG2.2.15 and HepG2.4A5 and the parental hepatoma
cell line HepG2 were incubated with different concentrations of palmitic and oleic
acid. In all 3 cell lines oleat did not affect cell viability up to a concentration
of 5µM. In contrast, palmitate dose-dependently induced toxic effects in all 3 cell-lines,
however, cytotoxic effects occurred at significantly lower palmitate concentration
in HBV producing cells. Assessment of intracellular lipid accumulation upon stimulation
with oleat revealed significantly higher levels of triglycerides and free fatty-acids
in HBV producing cell lines. In line with this, the expression of diacylglycerol acyltransferase
2 (DGAT2), which catalyzes the final step in hepatocyte triglyceride biosynthesis,
was significantly induced in HBV producing but not in the parental HepG2 cell line.
In contrast, expression of fatty acid synthase (FASN) and stearoyl-CoA desaturase1
(SCD1) did not differ significantly between cell lines indicating that the observed
difference in cellular lipid accumulation is not caused by de novo lipogenesis.
Conclusions: Our data indicate greater susceptibility to lipotoxicity as well as increased cellular
lipid accumulation of HBV producing cell lines in vitro. This novel in vitro model
allows studying the underlying mechanisms of this phenomenon, which may lead to new
therapeutic strategies in chronically HBV infected patients.
