Modulation of Autophagy as a Therapeutic Target in the Treatment of Metabolic Dysfunction-Associated Steatotic Liver disease: Evidence from Pharmacological, Nutritional, and Bioactive Compound Interventions

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health problem driven primarily by obesity and insulin resistance. Growing evidence indicates that hepatic autophagy dysfunction contributes to lipid accumulation, inflammation, and disease progression, making this process a promising therapeutic target. This review discusses pharmacological, nutritional, and bioactive compound interventions that modulate autophagy. Among pharmacological therapies, in experimental models, liraglutide and metformin reportedly activate the AMP-activated protein kinase/ mammalian target of rapamycin pathway, increasing the expression of microtubule-associated proteins 1A/1B light chain 3 form II and beclin 1, decreasing sequestosome 1 expression, and augmenting the nuclear translocation of transcription factor EB, indicating effective autophagy induction. Moreover, nutritional strategies, such as calorie restriction and intermittent fasting, regulate energy-sensing pathways and have been associated with improvements in steatosis, oxidative stress, and metabolic parameters. Bioactive compounds also modulate autophagy signaling and reduce hepatic lipid accumulation. Taken together, the evidence reinforces autophagy as a central mechanism by which various therapeutic approaches can attenuate MASLD, supporting the development of more effective and mechanism-based interventions.