Decanoylcarnitine improves liver mitochondrial dysfunction in hepatitis B virus infection by enhancing fatty acid β-oxidation

The incidence of metabolic-associated steatotic liver disease in patients with chronic hepatitis B is increasing annually; however, the interaction between hepatitis B virus (HBV) infection and lipid metabolism remains unclear. This study attempted to clarify whether fatty acid metabolism regulation could alleviate mitochondrial dysfunction caused by HBV infection. A public gene set of human livers was analyzed, and a proteomic analysis on mouse livers was conducted to explore metabolic disorders and affected organelles associated with HBV infection. The effect of decanoylcarnitine on fatty acid β-oxidation and mitochondria was investigated in vivo and in vitro. The pathways involved were shown by proteomic analysis and confirmed by Western blot. HBV infection could cause fatty acid β-oxidation disorder and mitochondrial dysfunction in vivo and in vitro. CPT1A overexpression could improve mitochondrial function in hepatocytes. Furthermore, decanoylcarnitine supplementation could activate CPT1A expression, thus improving fatty acid metabolism and repairing mitochondrial dysfunction. Proteomic analysis of mouse livers suggests that decanoylcarnitine stimulates the peroxisome proliferator-activated receptor (PPAR) signaling pathway, and PPARα was the most important among PPARs. Impaired fatty acid metabolism and mitochondrial dysfunction in hepatocytes caused by HBV infection could be partially restored by exogenous supplementation of decanoylcarnitine. This work elucidates the therapeutic potential of decanoylcarnitine in HBV infection and provides a new approach for diseases related to mitochondrial dysfunction.