Effect of lactate administration on mouse skeletal muscle under calorie restriction

Calorie restriction (CR) involves a reductions of calorie intake without altering the nutritional balance, and has many beneficial effects, such as improving oxidative metabolism and extending lifespan. However, CR decreases in skeletal muscle mass and fat mass in correlation with the reduction in food intake. Lactate is known to have potential as a signaling molecule rather than a metabolite during exercise. In this study, we examined the effects of the combination of caloric restriction and lactate administration on skeletal muscle adaptation in order to elucidate a novel role of lactate. We first demonstrated that daily lactate administration (equivalent to 1 g/kg of body weight) for 2 weeks suppressed CR-induced muscle atrophy by activating mammalian/mechanistic target of rapamycin (mTOR) signaling, a muscle protein synthesis pathway, and inhibited autophagy-induced muscle degradation. Next, we found that lactate administration under calorie restriction enhanced mitochondrial enzyme activity (citrate synthase and succinate dehydrogenase) and the expression of oxidative phosphorylation (OXPHOS) protein expression. Our results suggest that lactate administration under caloric restriction not only suppresses muscle atrophy but also improves mitochondrial function.