While the critical role of glycogen as a fuel source for ATP resynthesis during endurance exercise is undisputed, emerging evidence positions it as a potent regulator of molecular signaling pathways that govern skeletal muscle adaptation. This review synthesizes current knowledge on how glycogen availability influences these adaptive responses to both endurance and resistance exercise. Traditionally, glycogen depletion is known to impair endurance performance, and post-exercise carbohydrate ingestion is recommended to accelerate glycogen resynthesis and recovery. However, a paradigm shift is underway, with research demonstrating that chronic endurance training with low glycogen availability can amplify cellular signaling, leading to similar or even superior adaptations in mitochondrial biogenesis and exercise performance compared to training with high glycogen stores. In the context of resistance exercise, the role of glycogen is less clear. Initial investigations have focused on its impact on the acute anabolic response post-exercise. Nevertheless, the long-term effects of manipulating glycogen availability on phenotypic adaptations, such as hypertrophy and strength gains, remain a critical and unresolved question. This review underscores the dual role of glycogen, not only as an energy substrate but as a key signaling mediator, and highlights the need for further research to fully elucidate its mechanistic influence on muscle remodeling across different exercise modalities
