Metabolic stress and muscle mechanics: Acute response of isolated soleus and EDL muscles to prolonged fasting in mice with distinct muscle phenotypes.

Prolonged fasting impacts skeletal muscle by inducing atrophy, thereby limiting contractile capacity and altering tissue mechanical behavior. This study investigated the effects of 48 h of fasting (FAS) versus ad libitum food consumption (CON) on the mechanical properties of fast-twitch (extensor digitorum longus, EDL) and slow-twitch (soleus, SOL) muscles in three mouse strains with distinct muscle phenotypes: C57BL/6J (normal-sized), BEH+/+ (larger muscles), and BEH (myostatin-deficient with markedly larger muscles). Isolated SOL and EDL were subjected to 100 isometric-eccentric contraction cycles, and peak and specific force, rate of force development, fatigue, stiffness, and tangent modulus were assessed. Fasting significantly reduced muscle size and force production capacity (isometric and eccentric) across all strains (p<0.05). SOL muscles showed a greater decline in tetanic force (fatigue index: SOL 67% vs. EDL 33%, p<0.05), while BEH mice exhibited the steepest contractile impairment (p<0.05). Fasting also reduced stiffness and tangent modulus across all strains and muscle types (p<0.05). These findings demonstrate that fasting consistently impairs contractile and mechanical properties of skeletal muscle, with slow-twitch muscles and larger muscles phenotypes being particularly vulnerable. Muscle type and genetic background thus play key roles in determining the extent of functional decline under metabolic stress.