Abstract

The effects of lactate on muscle mass and regeneration were investigated using mouse skeletal muscle tissue and cultured C2C12 cells. Male C57BL/6J mice were randomly divided into (1) control, (2) lactate (1 mol/L in distilled water, 8.9 mL/g body weight)-administered, (3) cardio toxin (CTX)-injected (CX), and (4) lactate-administered after CTX-injection (LX) groups. CTX was injected into right tibialis anterior (TA) muscle before the oral administration of sodium lactate (five days/week for two weeks) to the mice. Oral lactate administration increased the muscle weight and fiber cross-sectional area, and the population of Pax7-positive nuclei in mouse TA skeletal muscle. Oral administration of lactate also facilitated the recovery process of CTX-associated injured mouse TA muscle mass accompanied with a transient increase in the population of Pax7-positive nuclei. Mouse myoblast-derived C2C12 cells were differentiated for five days to form myotubes with or without lactate administration. C2C12 myotube formation with an increase in protein content, fiber diameter, length, and myo-nuclei was stimulated by lactate. These observations suggest that lactate may be a potential molecule to stimulate muscle hypertrophy and regeneration of mouse skeletal muscle via the activation of muscle satellite cells.

Highlights

  • Muscle satellite cells are known as skeletal muscle-specific stem cells that reside between the basal lamina and sarcolemma of mature myo-fibers [1]

  • 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

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Summary

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 [2,3,4]. Activated muscle satellite cells proliferate and undergo differentiation into myoblasts. The myoblasts differentiate and fuse into preexisting myofibers or fuse to form new myofibers, which result in skeletal muscle hypertrophy or regeneration [5,6,7]. Exercise-associated stimuli, such as mechanical and heat stresses, are proposed to be potential stimuli to activate the regenerative process of injured skeletal muscle [11,12,13]. The mechanism of exercise-induced hypertrophy and regeneration of skeletal muscle is not fully elucidated

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