Alisol B alleviates MASLD by activating liver autophagy and fatty acid oxidation via Ces2a

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent global health issue characterized by excessive fat accumulation in the liver, often linked to obesity and metabolic syndrome. Despite advancements in understanding its pathogenesis, effective therapeutic strategies remain limited. This study investigates the potential of Alisol B, a natural compound from traditional Chinese medicine, in modulating lipid metabolism and autophagy in hepatocytes. We employed a combination of in vivo and in vitro approaches, including mouse models, cell culture assays, and transcriptomic profiling, to evaluate Alisol B's therapeutic efficacy against MASLD and elucidate its underlying mechanisms. Our findings reveal that Alisol B significantly reduces lipid accumulation and enhances fatty acid metabolism by upregulating Ces2a, a key regulator of lipid catabolism, as confirmed by RNA sequencing and Western blot analyses. Additionally, transcriptomic analysis indicates that Alisol B activates critical signaling pathways related to fatty acid metabolism and autophagy, including AMPK signaling. Importantly, in vitro studies demonstrate that Alisol B effectively reduces triglyceride levels in hepatocytes without compromising cell viability. Pharmacological inhibition of Ces2a further underscores its essential role in mediating Alisol B's therapeutic effects. These results suggest that Alisol B holds promise as a novel therapeutic agent for MASLD, warranting further exploration of its clinical applications and potential as a targeted treatment for metabolic disorders.