Induction of phospholipase A2 group 4C by HCV infection regulates lipid droplet formation

The involvement of phospholipid metabolism pathways in the pathogenesis of hepatitis C virus (HCV)-related liver diseases remains unclear. We found that <i>PLA2G4C</i> expression is upregulated through NF-κB and c-Myc activation upon HCV infection, and this upregulation is associated with a decrease in phosphatidylcholine species. The increased expression of <i>PLA2G4C</i> resulted in changes in the phospholipid composition of lipid droplets, led to the dissociation of lipolysis-related factors from the lipid droplet surface and the accumulation of lipid content within the droplets. These findings suggest that the disruption of the phospholipid metabolism pathway caused by HCV infection may contribute to the development of HCV-associated fatty liver. It would be interesting to determine whether alcohol- and/or metabolic dysfunction-associated steatohepatitis are also associated with increased PLA2 activity, altered phospholipid composition and decreased levels of ATGL and its cofactors in lipid droplet membranes.