SLC27A5 Inhibits HBV Replication Through Regulating FXR/SREBP1C/FASN/ACC1 Pathway in HepAD38 Cells

Hepatitis B virus (HBV) infection can lead to hepatitis B, which may eventually progress to cirrhosis or hepatocellular carcinoma (HCC). Host lipid metabolism plays a critical role in HBV replication, and HBV infection also impairs lipid homeostasis. The solute carrier family 27 member 5 (SLC27A5) gene, which encodes a long-chain fatty acid transporter and bile acid–CoA ligase, has been reported to be associated with cirrhosis and HCC. However, whether SLC27A5 influences HBV infection or replication remains unclear. In this study, the SLC27A5 gene was overexpressed or silenced in HepAD38 cells. Results show that SLC27A5 overexpressing suppresses HBV replication. Given the primary role of SLC27A5 in bile acid metabolism, we hypothesized that SLC27A5 might inhibit HBV replication via regulating the FXR/SREBP1C/FASN/ACC1 signaling pathway. Subsequent experiments confirmed that overexpression of SLC27A5 upregulated FXR expression levels and downregulated mRNA levels of the SREBP1C, FASN, and ACC1 genes. Consequently, lipid synthesis was suppressed in SLC27A5-overexpressing cells, with significantly reduced levels of lipid droplets and triglycerides. Furthermore, SLC27A5 might collaborate with Entecavir to inhibit HBV replication. In summary, we demonstrated that SLC27A5 inhibited HBV replication through regulating FXR/SREBP1C/FASN/ACC1 and decreasing lipid synthesis.