Myokines and Their Potential Protective Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Myokines are peptides released by the skeletal muscle that exert effects on peripheral tissues, activating metabolic or protective pathways against oxidative stress and inflammation. Many myokines increase their plasma levels after exercise, providing new insights into the role of physical activity in combating sarcopenia and preventing metabolic diseases, such as obesity, diabetes, and metabolic dysfunction associated with steatotic liver disease (MASLD). This review aims to discuss the roles of specific myokines in activating intracellular pathways in the liver to protect against steatosis and lipoperoxidation in MASLD. The progression of liver disease from steatosis to cirrhosis is partially driven by ferroptosis, an iron-dependent form of cell death linked to oxidative stress and lipoperoxidation. Exercise-induced myokines, such as irisin, have been shown to upregulate antioxidant enzymes such as glutathione (GSH) and glutathione peroxidase 4 (GPX4), which are crucial in reducing ferroptosis in hepatic tissues. This review provides a comprehensive perspective on the protective effects of myokines in the liver, particularly against lipid peroxidation and ferroptosis in MASLD, and highlights exercise as a therapeutic strategy to prevent the progression of this liver pathology.