Exercise therapy drives metabolic benefits on MASH Via modulating Hepatic Regulatory T-cells 4529

Abstract Description Background Metabolic dysfunction-associated steatohepatitis (MASH) is one of the leading causes of chronic liver diseases worldwide. While exercise therapy is known to alleviate MASH, the mechanisms remain unclear. Regulatory T cells (Tregs) play a crucial role in modulating inflammatory responses, but their role in exercise-mediated MASH improvement remains unclear. Methods Male 6-week-old mice were fed a Western Diet (WD) for 26 weeks, with normal diet (ND) mice as controls. Both groups underwent either sedentariness (Sed) or a 4-week treadmill exercise regimen (Ex). Body weight, liver weight to body weight ratio, liver ultrasound, blood glucose, ALT, cholesterol, triglycerides, hepatic Treg populations, immune microenvironment, and cytokine profiles were assessed. scRNA-seq was used to analyze Treg gene expression. Results MASH was successfully established, indicated by increased BW and LW/BW, liver injury, steatosis, and Treg accumulation. Compared with Sed, Ex ameliorated MASH in WD mice, evidenced by significantly decreased ALT, cholesterol, blood glucose and hepatic triglyceride levels. Ex also reduced Treg infiltration, increased CD8+T cells, and decreased monocyte infiltration and pro-inflammatory cytokines. scRNA-seq analysis revealed differential expression of ST2 and CTLA4 between Ex and Sed groups in Tregs. Summary: This study suggested a potential link between exercise-modulated Tregs attenuation and improvements in hepatic inflammation during MASH. Funding Sources R01GM137203 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)