**4. Discussion**

The present study demonstrated that oral lactate administration induced muscle hypertrophy accompanied with an increase of Pax7-positive nuclei in mouse TA muscle. In injured TA muscle, the increase of muscle mass and Pax7-positive nuclei population was stimulated by lactate administration. Furthermore, lactate-induced myotube formation including higher protein content, wider diameter, longer length, and more myo-nuclei were observed in C2C12 cells.

## *4.1. Muscle Hypertrophy*

In the present study, oral lactate administration increased TA muscle weight and fiber CSA in mice. This is the first report showing the effect of lactate on skeletal muscle mass in animals. Furthermore, the population of Pax7-positive nuclei in TA muscle was increased by lactate administration. Since the previous study using C2C12 skeletal muscle cells reported that extracellular lactate increased follistatin and decreased myostatin expressions involved in the proliferation of satellite cells [17,18], oral lactate administration-associated increase of blood lactate concentration may enhance the proliferation of muscle satellite cells. Recently, we demonstrated an extracellular lactate-associated increase in the diameter of C2C12 myo-tubes [19]. These observations sugges<sup>t</sup> that lactate administration, which could increase blood lactate levels, stimulated the hypertrophy of skeletal muscle with the activation of muscle satellite cells. Training with a blood flow restriction, which is exercise with vascular occlusion, is known to increase muscle size [28,29] and the blood lactate level [29,30] in humans. Therefore, there is a possibility that the blood lactate level may contribute to muscle size following occlusion training.
