Anti-adipogenic and antiviral effects of l-carnitine on hepatitis C virus infection.

Background and Aims Hepatitis C virus (HCV) has been reported to hijack fatty acid metabolism in infected hepatocytes, taking advantage of lipid droplets for virus assembly. In this study, we analyzed the anti-HCV activity of L-carnitine, a substance involved in the transport of fatty acids into mitochondria. Methods JFH-1 or HCV replicon-transfected Huh7.5.1 cells were treated with or without L-carnitine to examine its anti-HCV effects. The effects of L-carnitine on HCV entry, HCV-induced adipogenesis and lipid droplet formation, and HCV-induced oxidative stress were examined. Results Treatment of JFH-1-infected cells with L-carnitine inhibited HCV propagation in a concentration-dependent manner. In contrast, L-carnitine had no anti-HCV activity in the HCV replicon system, which is lacking viral assembly. In addition, L-carnitine did not affect HCV entry. However, L-carnitine treatment decreased intracellular lipid droplets, which are crucial for HCV assembly in JFH-1-infected cells. The expression level of CPT-1 was decreased in JFH-1-infected cells, and L-carnitine treatment restored this expression. HCV-infected cells exhibited increased production of reactive oxygen species and glutathione oxidation. L-Carnitine decreased oxidative stress induced by JFH-1-infection, as shown by glutathione/glutathione disulfide assays and MitoSOX staining. Conclusions L-Carnitine exhibited anti-HCV activity, possibly by inhibiting HCV assembly and through its anti-adipogenic activity in HCV-infected cells. Moreover, L-carnitine has antioxidant properties in HCV-infected hepatocytes. Overall, these results indicated that L-carnitine may be an effective adjunctive agent in antiviral therapies to treat chronic hepatitis C. This article is protected by copyright. All rights reserved