Effects of lactate administration on mitochondrial enzyme activity and monocarboxylate transporters in mouse skeletal muscle

Growing evidence shows that lactate is not merely an intermediate metabolite, but also a potential signaling molecule. However, whether daily lactate administration induces physiological adaptations in skeletal muscle remains to be elucidated. In this study, we first investigated the effects of daily lactate administration (equivalent to 1 g/kg of body weight) for 3 weeks on mitochondrial adaptations in skeletal muscle. We demonstrated that 3‐week lactate administration increased mitochondrial enzyme activity (citrate synthase, 3‐hydroxyacyl CoA dehydrogenase, and cytochrome c oxidase) in the plantaris muscle, but not in the soleus muscle. MCT1 and MCT4 protein contents were not different after 3‐week lactate administration. Next, we examined whether lactate administration enhances training‐induced adaptations in skeletal muscle. Lactate administration prior to endurance exercise training (treadmill running, 20 m/min, 60 min/day), which increased blood lactate concentration during exercise, enhanced training‐induced mitochondrial enzyme activity in the skeletal muscle after 3 weeks. MCT protein content and blood lactate removal were not different after 3‐week lactate administration with exercise training compared to exercise training alone. In a single bout experiment, lactate administration did not change the phosphorylation state of AMPK, ACC, p38 MAPK, and CaMKII in skeletal muscle. Our results suggest that lactate can be a key factor for exercise‐induced mitochondrial adaptations, and that the efficacy of high‐intensity training is, at least partly, attributed to elevated blood lactate concentration. Lactate had been considered a waste product of glycolysis, but is now recognized as an oxidizable substrate, as well as a potential signaling molecule that induces beneficial adaptations in various tissues. This study showed that daily lactate administration with or without endurance exercise training enhanced mitochondrial enzyme activity in mouse skeletal muscle. This suggests that lactate is a key factor for exercise‐induced mitochondrial adaptations.