Non‐Nutritive Artificial Sweeteners Aspartame and Acesulfame‐K Ameliorate Metabolic Dysfunction‐Associated Steatotic Liver Disease in Male Ldlr −/− Mice

Aspartame and acesulfame‐K are commonly used non‐nutritive artificial sweeteners, but their impacts on cardiovascular disease and metabolic dysfunction‐associated fatty liver disease (MASLD) are unclear. In this study, we evaluated the impacts of aspartame and acesulfame‐K on MASLD and atherosclerosis in male Ldlr −/− mice fed an AMLN diet. Both sweeteners reduced body weight and improved hepatic steatosis and fibrosis. However, 20‐week acesulfame‐K intake increased atherosclerotic plaque area, whereas aspartame showed no such effect. Transcriptomic analysis revealed altered pathways linked to lipid metabolism and inflammation. These findings suggest that both sweeteners ameliorate MASLD but that acesulfame‐K may slightly increase atherosclerosis in this atherosclerosis‐MASLD comorbidity model.