Lactate administration does not affect denervation-induced loss of mitochondrial content and muscle mass in mice

Abstract

Lactate is considered to be a signaling molecule that induces mitochondrial adaptation and muscle hypertrophy. The purpose of this study was to examine whether lactate administration attenuates denervation-induced loss of mitochondrial content and muscle mass. Eight-week-old male Institute of Cancer Research mice underwent unilateral sciatic nerve transection surgery. The contralateral hindlimb served as a sham-operated control. From the day of surgery, mice were injected intraperitoneally with PBS or sodium lactate (equivalent to 1 g·kg^-1 body weight) once daily for 9 days. After 10 days of denervation, gastrocnemius muscle weight decreased to a similar extent in both the PBS- and lactate-injected groups. Denervation significantly decreased mitochondrial enzyme activity, protein content, and MCT4 protein content in the gastrocnemius muscle. However, lactate administration did not have any significant effects. The current observations suggest that daily lactate administration for 9 days does not affect denervation-induced loss of mitochondrial content and muscle mass.

Keywords: denervation; lactate; mitochondria; skeletal muscle.

Fig. 1

Animal characteristics. Body weight (A), energy intake (B), gastrocnemius muscle weight (C), and relative gastrocnemius weight to body weight (D) in the Experiment 1. Data are presented as mean ± SEM (n = 10). Student's t‐test or two‐way ANOVA (denervation × lactate administration) was used for statistical evaluation. n.s., not significant. **P < 0.01: main effect of denervation.

Fig. 2

Mitochondrial enzyme activities. Maximal activities of CS (A), β‐HAD (B), and COX (C) in the gastrocnemius muscle (Experiment 1). Data are presented as means ± SEM (n = 10). Two‐way ANOVA (denervation × lactate administration) was used for statistical evaluation. **P < 0.01: main effect of denervation.

Fig. 3

Mitochondrial protein contents. Protein contents of PGC‐1α (A), mitochondrial respiratory chain subunits (B–G), and CS (H) in the gastrocnemius muscle (Experiment 1). Data are presented as means ± SEM (n = 10). Two‐way ANOVA (denervation × lactate administration) was used for statistical evaluation. **P < 0.01: main effect of denervation.

Fig. 4

Protein content of mitochondrial dynamics. Protein contents of Mfn2 (A), Opa1 (B), Fis1 (C), and Drp1 (D) in the gastrocnemius muscle (Experiment 1). Two‐way ANOVA (denervation × lactate administration) was used for statistical evaluation. Data are presented as means ± SEM (n = 10). **P < 0.01: main effect of denervation.

Fig. 5

MCT protein contents. Protein contents of MCT1 (A) and MCT4 (B) in the gastrocnemius muscle (Experiment 1). Two‐way ANOVA (denervation × lactate administration) was used for statistical evaluation. Data are presented as means ± SEM (n = 10). **P < 0.01: main effect of denervation.

Fig. 6

Protein phosphorylation. Phosphorylation status of mTOR (A), p70S6K (B), ERK (C), and MEK (D) in the gastrocnemius muscle at 60 min after lactate administration (Experiment 2). Data are presented as means ± SEM (n = 10 or 11). Student's t‐test was used for statistical evaluation.