King Grub
2018-11-26, 10:38
Lactate is a metabolic substrate mainly produced in muscles, especially during exercise. Recently, it was reported that lactate affects myoblast differentiation; however, the obtained results are inconsistent and the in vivo effect of lactate remains unclear. Our study thus aimed to evaluate the effects of lactate on myogenic differentiation and its underlying mechanism. The differentiation of C2C12 murine myogenic cells was accelerated in the presence of lactate and, consequently, myotube hypertrophy was achieved. Gene expression analysis of myogenic regulatory factors showed significantly increased myogenic determination protein (MyoD) gene expression in lactate-treated cells compared with that in untreated ones. Moreover, lactate enhanced gene and protein expression of myosin heavy chain (MHC). In particular, lactate increased gene expression of specific MHC isotypes, MHCIIb and IId/x, in a dose-dependent manner. Using a reporter assay, we showed that lactate increased promoter activity of the MHCIIb gene and that a MyoD binding site in the promoter region was necessary for the lactate-induced increase in activity. Finally, peritoneal injection of lactate in mice resulted in enhanced regeneration and fiber hypertrophy in glycerol-induced regenerating muscles.
In conclusion, in this study, we demonstrated that a sustained elevation of lactate would support myogenic differentiation, as well as muscle fiber hypertrophy. Regarding the mechanism involved in this, our findings suggest a novel mechanism in which increased MyoD expression, facilitated by lactate, might play a critical role in the increase in predominantly fast-twitch-type MHCs. A notable finding is that the effect of lactate was probably enhanced through auto-regulatory loops associated with this molecule. Blood levels of lactate after exercise can reach those used in our study. Thus, our findings are potentially important for considering efficient exercise-based strategies to maintain muscle volume and/or to induce muscle hypertrophy.
Lactate Promotes Myoblast Differentiation and Myotube Hypertrophy via a Pathway Involving MyoD In Vitro and Enhances Muscle Regeneration In Vivo. Int. J. Mol. Sci. 2018, 19(11), 3649.
https://www.mdpi.com/1422-0067/19/11/3649/htm
In conclusion, in this study, we demonstrated that a sustained elevation of lactate would support myogenic differentiation, as well as muscle fiber hypertrophy. Regarding the mechanism involved in this, our findings suggest a novel mechanism in which increased MyoD expression, facilitated by lactate, might play a critical role in the increase in predominantly fast-twitch-type MHCs. A notable finding is that the effect of lactate was probably enhanced through auto-regulatory loops associated with this molecule. Blood levels of lactate after exercise can reach those used in our study. Thus, our findings are potentially important for considering efficient exercise-based strategies to maintain muscle volume and/or to induce muscle hypertrophy.
Lactate Promotes Myoblast Differentiation and Myotube Hypertrophy via a Pathway Involving MyoD In Vitro and Enhances Muscle Regeneration In Vivo. Int. J. Mol. Sci. 2018, 19(11), 3649.
https://www.mdpi.com/1422-0067/19/11/3649/htm