Myostatin in Obesity: A Molecular Link Between Metabolic Dysfunction and Musculotendinous Remodeling

TL;DR

This paper explores how myostatin, a protein linked to muscle regulation, contributes to obesity-related muscle and tendon issues, suggesting it could be a key target for treatment.

Contribution

The paper introduces myostatin's role in musculotendinous remodeling and metabolic dysfunction in obesity, beyond its known effects on muscle mass.

Findings

Elevated myostatin levels in obesity are linked to insulin resistance and muscle atrophy.

Myostatin inhibition improves glucose homeostasis and increases lean mass in preclinical studies.

Myostatin affects extracellular matrix organization and tissue fragility in musculotendinous systems.

Abstract

Obesity is increasingly recognized not only as a metabolic disorder but also as a condition marked by the structural and functional deterioration of skeletal muscle and tendon tissues. Central to this process is the dysregulation of the extracellular matrix (ECM) resulting in fibrosis and ectopic fat accumulation, factors that contribute to impaired tissue mechanics. Myostatin (GDF-8), a member of the TGF-β superfamily, is known as a negative regulator of muscle mass. It can also mediate interaction between adipose and other tissues including muscles and tendons. In obesity, elevated myostatin levels have been reported to be associated with insulin resistance, muscle atrophy, and activation of SMAD2/3 signaling, while experimental and preclinical studies indicate that myostatin inhibition can improve glucose homeostasis and increase lean mass. Emerging evidence suggests that myostatin also plays a critical role in muscle ECM and tendon remodeling. Restoring its physiological levels may help reverse ECM disorganization and reduce tissue fragility associated with musculotendinous dysfunction. This review highlights the multifaceted role of myostatin in obesity, beyond its role in muscle catabolism, to include modulation of structural integrity, metabolism, and mechanical adaptability of the musculotendinous system. Understanding how myostatin responds to metabolic stress and affects biomechanical remodeling offers novel insights into obesity-related muscle and tendon dysfunction.

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