The myokine musclin in metabolic syndrome: Pathological links and exercise interventions

Since its identification in 2004, the myokine Musclin, a skeletal muscle-specific secretory factor, has garnered increasing attention in the fields of metabolism and exercise medicine due to its pleiotropic regulatory functions. This review proposes and substantiates the central thesis that Musclin acts as a "bidirectional hub" connecting exercise and metabolic homeostasis. Under physiological conditions, the pulsatile secretion of Musclin promotes mitochondrial biogenesis and enhances exercise endurance. In contrast, during pathological states, its overexpression exacerbates metabolic disorders by interfering with insulin signaling, inducing endoplasmic reticulum stress (ERS), and suppressing adipose thermogenesis. A body of evidence indicates that the expression and function of Musclin are precisely regulated by genetic, nutritional, and exercise-related factors, underscoring its pivotal role in the systemic metabolic network. Although its elevated levels may be perceived as a compensatory response in certain contexts, gain-of-function experiments and other evidence posit that Musclin primarily acts as a "pathological driver," demonstrating context-dependent effects in obesity, type 2 diabetes mellitus (T2DM), hypertension, and other components of metabolic syndrome (MetS). Current research in the field faces challenges, including sample heterogeneity, lack of standardized detection methods, and a translational gap between animal models and human diseases. Therefore, this review systematically integrates the molecular characteristics, pathophysiological effects, and exercise adaptation mechanism of Musclin, and reveals its "bidirectional hub" role in metabolic homeostasis.