Lactate Administration Increases Skeletal Muscle Synthesis in Mice

PURPOSE: Lactate, secreted by skeletal muscle during exercise, had been known as fatigue substance. However, several physiological roles of lactate have been revealed in the last decades, and previous studies reported that lactate treatment increased protein synthesis factors in skeletal muscle. Nevertheless, underlying molecular mechanisms of exogenous lactate on protein synthesis and degradation remain unknown, and there was no study that confirm long-term lactate administration with exercise training. Therefore, the purpose of study is to investigate the effect of long-term exogenous lactate administration and lactate administration with exercise training on the skeletal muscle synthesis and degradation. METHODS: 32 mice were randomly divided into four groups: sedentary + saline (Sed/Con), sedentary + lactate (Sed/Lac), exercise training + saline (Ex/Con), and Exercise training + lactate (Ex/Lac). Exercise training (VO2 max 70%) and lactate administration (3 g/kg sodium lactate) performed 5 days a week. The timing of lactate administration was immediately after every exercise training, and saline administration groups were given same volume of saline as lactate. After 5 weeks, mice were sacrificed and immediately obtained skeletal muscle and blood. To confirm the effect of lactate on protein synthesis (IGF receptor, Akt and mTOR phosphate/total) and degradation (MuRF1, MAFbx1, FOXO1), mRNA and protein expression analyzed respectively plantaris and extensor digitorum longus. Blood parameters of lactate, insulin, IGF1, and glucose were measured. RESULTS: Skeletal muscle weight tended to higher Sed/Lac than Sed/Con, but Sed/Lac had significantly supplement effects compared to Sed/Con in only gastrocnemius weight (p = .000). Blood IGF1 showed that Sed/Lac was significantly lower than Sed/Con (p = .039) and Ex/Lac (p = .007). mRNA of IGF receptor had only exercise effects (p = .000). mRNA of Akt and mTOR showed that Sed/Lac was significantly higher than Sed/Con (respectively, p = .000 and p = .043). Protein expression of MuRF1, Sed/Lac was significantly lower than Sed/Con (p = .046), but exercise training effects was found saline groups (Sed/Con vs Ex/Con; p = .001). CONCLUSION: This study showed that long-term lactate administration had positive effects on Akt / mTOR and MuRF1. Especially, it was confirmed that long-term lactate administration increased skeletal muscle mass in mice. Hence, we suggest that long-term lactate administration increases skeletal muscle synthesis and that lactate administration can be used as supplement for sarcopenia. Nevertheless, this study did not confirm synergistic effects of lactate administration with exercise training. It is suggested that post-exercise lactate administration, unlike lactate administration at rest state, affects energy metabolism rather skeletal muscle synthesis. Therefore, future study would be necessary to investigate lactate administration timing with exercise training. © FASEB.