Decanoylcarnitine Enhances Fatty Acid β-Oxidation and Mitochondrial Function in HBV-Infected Liver Cells
Overview
Hepatitis B virus (HBV) infection impairs fatty acid β-oxidation and mitochondrial function in hepatocytes, contributing to metabolic dysfunction. Supplementation with decanoylcarnitine activates CPT1A and the PPARα signaling pathway, restoring mitochondrial function and improving lipid metabolism in HBV-infected liver cells.
Background
Chronic hepatitis B virus infection and metabolic-associated steatotic liver disease (MASLD) are leading causes of liver cirrhosis and hepatocellular carcinoma worldwide. The prevalence of MASLD among patients with chronic hepatitis B has increased significantly, exacerbating liver disease progression. Fatty acid β-oxidation (FAO) in mitochondria is critical for energy production, but HBV infection disrupts mitochondrial function and lipid metabolism. Understanding the interaction between HBV and fatty acid metabolism may reveal novel therapeutic strategies to mitigate liver damage.
Data Highlights
HBV infection causes fatty acid β-oxidation disorder and mitochondrial dysfunction in hepatocytes both in vivo and in vitro. Decanoylcarnitine supplementation activates CPT1A expression and the PPARα signaling pathway, improving mitochondrial respiratory function and reducing lipid accumulation. Proteomic analyses confirm these metabolic improvements in mouse liver models.
Key Findings
HBV infection impairs mitochondrial fatty acid β-oxidation and causes lipid accumulation in hepatocytes.
Overexpression of CPT1A improves mitochondrial function in HBV-infected hepatocytes.
Decanoylcarnitine supplementation activates CPT1A and enhances fatty acid metabolism.
Decanoylcarnitine stimulates the PPAR signaling pathway, with PPARα playing a central role.
Exogenous decanoylcarnitine partially restores mitochondrial function and lipid metabolism disrupted by HBV.
These effects were demonstrated through proteomic analysis, Western blot, and in vitro and in vivo models.
Clinical Implications
Decanoylcarnitine supplementation represents a promising therapeutic approach to mitigate mitochondrial dysfunction and metabolic disturbances in patients with chronic HBV infection. Enhancing fatty acid β-oxidation via CPT1A activation and PPARα signaling may reduce liver lipid accumulation and improve hepatocyte energy metabolism, potentially slowing disease progression and improving outcomes.
Conclusion
This study identifies decanoylcarnitine as a novel agent that improves mitochondrial function and fatty acid metabolism in HBV-infected liver cells. Targeting acylcarnitine metabolism offers a new therapeutic avenue for managing HBV-related liver disease and mitochondrial dysfunction.
References
Wang et al. 2024 -- Decanoylcarnitine Enhances Fatty Acid β-Oxidation and Mitigates Mitochondrial Dysfunction in Liver Cells Infected with Hepatitis B Virus
