Chitosan and chito-oligosaccharides as multifunctional therapeutics for metabolic dysfunction-associated steatotic liver disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously called metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic fatty liver disease (NAFLD), has emerged as a leading cause of chronic liver injury worldwide, driven by insulin resistance, oxidative stress, inflammation, and gut dysbiosis. Current pharmacotherapies remain limited in efficacy and safety, underscoring the need for alternative strategies. Chitosan and chito-oligosaccharides represent promising candidates owing to their multifunctional bioactivities and excellent safety profiles. Evidence from cellular, animal, and preliminary clinical studies indicates that these compounds exert protective effects through coordinated modulation of multiple pathophysiological pathways. They enhance intestinal barrier function and promote the growth of beneficial gut microbiota, leading to reduced lipopolysaccharide translocation and improved hepatic inflammation via gut-liver axis regulation. Simultaneously, chitosan and chito-oligosaccharides activate AMP-activated protein kinase and PPARαsignaling, inhibit lipogenic enzymes, and upregulate fatty acid oxidation, thereby restoring lipid homeostasis. Their antioxidant capacity is mediated through nuclear factor erythroid 2-related factor 2 activation, while inflammatory cascades involving NF-κB and cytokine overproduction are suppressed. Collectively, these findings position chitosan and chito-oligosaccharides as sustainable therapeutics targeting multiple metabolic and inflammatory pathways in MASLD.