Protective effects of dopamine against non-alcoholic steatohepatitis via inhibiting p65 pathways in vivo and in vitro

Abstract

Introduction: Currently, the role and mechanism of dopamine in non-alcoholic steatohepatitis (NASH) remains unclear.

Methods: In vitro experiments utilized FFA and LPS to establish NASH cell models, while a fibrotic cell model was created using TGFβ1 to investigate the impact of dopamine on cellular lipid metabolism, inflammation, and fibrosis. In vivo experiments involved the use of MCD and HFD diets to induce NASH in mouse models for observing the effects of dopamine on NASH disease progression.

Results: Our study showed that dopamine significantly downregulated the expression levels of Caspase 1, IL-1β and IL18 in the HepG2 NASH cell model. In addition, dopamine could inhibit the TGF-β1-induced accumulation of collagen I and α-SMA in LX2 cells. In vivo experiments have shown that dopamine attenuation in mice is associated with MCD diet-induced and HFD-induced steatohepatitis. Mechanically, dopamine inhibits the p65 signaling pathway in NASH.

Conclusion: In conclusion, the present study demonstrates the role of dopamine in ameliorating the symptoms of NASH and provides a direction for future research on the application of the dopaminergic system to liver disease.

Keywords: dopamine; inflammasomes; non-alcoholic steatohepatitis (NASH); p65 pathway.