Adenosine monophosphate-activated protein kinase: A golden mediator of exercise in metabolic dysfunction-associated...

Metabolic diseases represent a major threat to human health and are largely associated with excessive energy intake and insufficient energy expenditure. Increasing evidence indicates that obesity, diabetes, metabolic dysfunction-associated fatty liver disease, sarcopenia, Alzheimer's disease, and cancer are closely associated with metabolic dysfunction. Extensive clinical studies and therapeutic strategies have been developed for the prevention and treatment of these disorders. Among these approaches, targeted regulation of cellular energy homeostasis has emerged as a widely recognized strategy, with adenosine monophosphate-activated protein kinase (AMPK) identified as an important therapeutic target for metabolic disease intervention. With the growing development of sports medicine, exercise has become a preferred non-pharmacological approach for the prevention and management of metabolic dysfunction-related diseases, with its beneficial effects largely mediated through AMPK activation. However, the mechanisms by which exercise modulates AMPK and its subtypes in different tissues and diseases remain incompletely understood. Therefore, this narrative review retrieved English-language literature published up to May 2026 from the PubMed, Web of Science, and Scopus databases. A search strategy was constructed using the terms "AMPK", "exercise", "obesity", "diabetes", "NAFLD/MASLD", "sarcopenia", and "Alzheimer's disease" and the corresponding tissues associated with these metabolic diseases. A comprehensive analysis was conducted focusing on AMPK and its subtypes. In this narrative review, we synthesize current research on how exercise modulates AMPK in different tissues and subtype-specific functions, summarizing and analyzing existing evidence that may provide a theoretical basis for subtype-targeted therapeutic strategies (including exercise therapy and pharmacological therapy) for metabolic dysfunction-related diseases.