Development of an in vitro model to study hepatitis C virus effects on hepatocellular lipotoxicity and lipid metabolism

Publication date: Available online 19 August 2018Source: Pathology - Research and PracticeAuthor(s): Leandra Koletzko, Abdo Mahli, Claus HellerbrandAbstractHepatic steatosis is common in patients infected with hepatitis C virus (HCV). Particularly in patients infected with non-genotype 3 HCV, hepatic steatosis is closely related to factors of the metabolic syndrome such as hyperlipidemia. However, the molecular mechanisms involved in this "metabolic" steatosis in non-3 genotype HCV infections are not well understood. Here, we aimed to develop an in vitro model to study the effect of genotype 1 HCV infection on hepatic lipotoxicity and lipid metabolism. Cellular lipid accumulation was induced in Huh-7 hepatoma cells transfected with HCV genotype 1b replicon (HCV+) by incubation with increasing doses of palmitic acid (C16:0) or oleic acid (C18:1 n-9) complexed to albumin mimicking hyperlipidemic conditions. Mock transfected hepatoma cells (HCV-) were used as controls. Incubation with oleic acid concentrations as high as 0.5 mM did not induce toxic effects in HCV+ or HCV- cells. In contrast, incubation with palmitic acid caused dose-dependently cytotoxic effects which were more pronounced in HCV+ compared to HCV- cells. Further analysis with subtoxic palmitic and oleic acid concentrations revealed a higher uptake of fatty acids and intracellular triglyceride accumulation in HCV+ compared to HCV- cells. Carnitine palmitoyltransferase I (CPT1) expression, indicative of mitochond...
Source: Pathology Research and Practice - Category: Pathology Source Type: research