The Effect of Stevioside on Hepatic Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Stevioside is a widely used natural non-nutritive sweetener derived from Stevia rebaudiana; however, its effects on MASLD and the underlying molecular mechanisms remain unclear. This study aimed to elucidate the effects and mechanisms of stevioside on MASLD, based on the high-fat diet-induced mice model and palmitic acid-treated hepatocyte model. We found that stevioside significantly alleviated hepatic steatosis in MASLD mice and reduced plasma ALT and AST levels and hepatic triglyceride and total cholesterol. In palmitic acid-induced hepatocytes, stevioside significantly reduced intracellular lipid droplet content and upregulated the protein levels of p-AMPK, PPARα, and EHHADH. Pharmacological inhibition of AMPK and PPARα revealed that stevioside regulated PPARα expression and downstream EHHADH expression in an AMPK-dependent manner. To conclude, stevioside significantly improved hepatic steatosis in MASLD by activating the AMPK/PPARα/EHHADH pathway, potentially generating novel evidence to help control the escalating disease burden of MASLD from the perspective of natural sweetener.