In recent years, accumulating experimental and clinical evidence has highlighted the activation of AMP-activated protein kinase (AMPK) as a promising strategy for enhancing metabolic health, particularly in promoting weight loss and managing obesity-associated disorders such as insulin resistance (IR), non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH). This evidence concerns the gene PRKAA2 and metabolic dysfunction-associated steatotic liver disease.