Lactate supplementation modulates molecular and functional responses during chronic neuromuscular electrical stimulation in male rats.

Lactate is increasingly recognized as a signaling molecule that modulates muscle plasticity. We examined the effects of oral L-sodium lactate supplementation on skeletal muscle adaptation to chronic neuromuscular electrical stimulation (NMES) in rats. Male Wistar rats received oral lactate or water before either a single NMES session (acute) or repeated sessions over 2 weeks (chronic). We assessed muscle weight, strength, myonuclear-associated protein expression (PCM1), protein synthesis (puromycin incorporation), signaling responses (mechanistic target of rapamycin pathway), and mitochondrial-related protein expression (PGC-1α, OXPHOS, and citrate synthase). The oxidative soleus and glycolytic plantaris muscles were analyzed. Lactate supplementation was associated with greater increases in muscle mass and torque during chronic NMES, particularly in the soleus. PCM1 abundance and myofibrillar puromycin incorporation were higher in the lactate-supplemented group, although there were no significant changes in c-Myc or rpS6. PGC-1α expression was elevated in the plantaris muscle, indicating muscle-type-specific mitochondrial modulation. However, the expression levels of the lactate transporters (MCT1 and MCT4) and GPR81 remained largely unchanged in response to oral lactate. Collectively, these findings suggest that oral lactate is associated with distinct molecular signatures and functional outcomes during chronic NMES in a muscle type-dependent manner, warranting further studies using morphological and muscle-specific functional assessments.