Muscle Insulin Resistance Elicits Muscle Atrophy in Obesity.

This review comprehensively highlights the molecular and cellular pathways that link insulin resistance (IR) to muscle atrophy. Skeletal muscle IR is a key driver of muscle atrophy in obesity. It disrupts metabolic homeostasis, leading to impaired glucose uptake and utilization. Crucially, IR shifts the balance in skeletal muscle from anabolic to catabolic processes by simultaneously inhibiting protein synthesis and promoting proteolysis, resulting in a progressive decline of muscle mass and function. This review summarizes how defective insulin signaling activates a cascade of intracellular events that accelerate muscle wasting in obese individuals. The nexus between IR and muscle atrophy in obesity involves multiple interconnected mechanisms, including mitochondrial dysfunction, elevated inflammation and oxidative stress, and compromised satellite cell function-essential for muscle repair and regeneration. The prevalence of IR, which rises with age and is exacerbated by sedentary behavior and poor nutrition, underscores the importance of understanding these signaling pathways. Elucidating these mechanisms is critical for developing effective interventions to combat muscle loss and enhance metabolic health in the obese population. © 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.