Chitosan lactate mitigates metabolic-associated fatty liver disease via TGR5-mediated anti-inflammatory mechanisms and the gut-hepatic-bile acid axis

As a derivative of chitosan, chitosan lactate (CTL) not only maintains the good biological activity of chitosan, but also effectively improves the water-insoluble characteristics of chitosan. We used CTL to intervene in metabolic-related fatty liver disease (MAFLD) model mice, observed the effect of CTL on MAFLD mice, and detected the expression of TGR5-PKA pathway and classical inflammatory pathway-related proteins in mouse liver. The intestinal flora and bile acids of mice were further analyzed. The results showed that CTL had good therapeutic activity against MAFLD, inhibited the activation of NF-κB inflammatory pathway in liver through TGR5-PKA-IκBα-p65 and TGR5-PKA-CREB pathways, and improved the intestinal flora structure and bile acid profile of MAFLD mice. This study shows that CTL improves high-fat diet-induced liver inflammation in MAFLD mice by regulating liver inflammation pathways, intestinal flora and bile acid profiles, laying a foundation for the development of natural drugs for the treatment of MAFLD. • Chitosan lactate demonstrated good MAFLD therapeutic activity. • Chitosan lactate inhibited the activation of liver NF-κB inflammatory pathways through the TGR5-PKA-IκBα-p65 and TGR5-PKA-CREB pathways. • Chitosan lactate modulates intestinal flora and bile acids in MAFLD mice.