**1. Introduction**

Muscle satellite cells are known as skeletal muscle-specific stem cells that reside between the basal lamina and sarcolemma of mature myo-fibers [1]. Muscle satellite cells, which express the paired box transcription factor 7 (Pax7), are normally quiescent but become activated in response to exercise or injury [2–4]. Activated muscle satellite cells proliferate and undergo differentiation into myoblasts. Then the myoblasts differentiate and fuse into preexisting myofibers or fuse to form new myofibers, which result in skeletal muscle hypertrophy or regeneration [5–7].

Muscle satellite cells are considered to play a crucial role in exercise-associated muscle hypertrophy in human skeletal muscles [6,8] even though the studies using rodent models indicated that satellite cells may not contribute to exercise-associated hypertrophy of skeletal muscle [9,10]. Furthermore, exercise-associated stimuli, such as mechanical and heat stresses, are proposed to be potential stimuli to activate the regenerative process of injured skeletal muscle [11–13]. However, the mechanism of exercise-induced hypertrophy and regeneration of skeletal muscle is not fully elucidated.

Recent studies demonstrate that the number of biologically active molecules, so-called myokines, are released from resting as well as contracting skeletal muscle cells [14]. It is generally accepted that intensive exercise induces the release of lactate from contracting skeletal muscle. Extracellular lactate is re-uptaken by skeletal muscle to utilize it for an energy source [15,16]. On the other hand, the previous study using C2C12 skeletal muscle cells showed that a high level of extracellular lactate changed the expression of follistatin and myostatin [17], which regulate the proliferation of muscle satellite cells [18]. Furthermore, we recently demonstrated extracellular lactate-associated C2C12 myotube hypertrophy by activating the anabolic intracellular signals, such as p42/44 extracellular signal-regulated kinase-1/2 (ERK1/2) pathway [19], which stimulates muscle cell proliferation and differentiation [20–22]. Judging from published results, we hypothesize that increasing extracellular lactate level, which is generally induced by intensive exercise, may induce muscle hypertrophy as well as regeneration of injured skeletal muscle by activating muscle satellite cells.

In the present study, we investigated the effects of oral lactate administration on hypertrophy and regeneration in mouse skeletal muscle. Since previous studies have reported that an increase of satellite cells, which is caused by extracellular stimuli including electrical and heat stimulation [11,23], facilitated muscle regeneration, we evaluated the population of satellite cells following lactate administration. The effects of lactate on the formation of myotubes were also investigated by using cultured C2C12 cells.

#### **2. Materials and Methods**
