Resistance training induces not only muscle hypertrophy but also mitochondrial adaptation (Kitaoka et al. 2016). However, it is also known that resistance training-induced mitochondrial adaptation is limited and smaller than endurance training-induced mitochondrial adaptation (Wilkinson et al. 2008).
β-guanidinopropionic acid (β-GPA) inhibits creatine transport into the cell and decreases creatine in skeletal muscle. Previous studies have reported that β-GPA activates mitochondrial biogenesis and increases mitochondrial content markers in skeletal muscle (Williams et al. 2009).
However, the effects of β-GPA on resistance training are not clear. Therefore, the aim of this study was to investigate the effects of β-GPA on resistance training adaptation in rat skeletal muscle.
This experiment was approved by the Ethics Committee for Animal Experiments at Ritsumeikan University (BKC2022-009). 8-week-old male SD rats were randomized to (1) placebo group or (2) β-GPA group (n = 5/group). β-GPA (1000 mg/kg) was administered once daily in the β-GPA group by oral ingestion by a sonde. Resistance exercise was performed according to a previous study (Takegaki et al. 2019). Briefly, the ankle joint was positioned at 90 degrees, and a 3-second maximal isometric contraction was performed 10 times with a 7-second interval (1 set), for a total of 5 sets. Resistance exercise was performed only on the right gastrocnemius muscle and the left gastrocnemius muscle was treated as a resting sample. During exercise, rats were anesthetized with 2% concentration of isoflurane. Resistance exercise was performed for a total of 12 sessions, and 48 hours after the last exercise session, rats were anesthetized and gastrocnemius muscles were removed. Western blotting was used to evaluate the expression levels of proteins involved in mitochondrial biogenesis. Two-way ANOVA was used for statistical analysis, and multiple comparisons were made only when an interaction was observed. Unpaired t-test was only used for the analysis of the % change in muscle mass.
A significant interaction was found for protein expression levels of PGC-1α, a key regulator of mitochondrial biogenesis (p < 0.05). Multiple comparisons showed that PGC-1α protein expression was significantly higher in β-GPA + exercised leg (+82.5% vs placebo + rested leg) than in the placebo + exercised leg (+34.3% vs placebo + rested leg) (p < 0.05). A significant interaction was also observed in total OXPHOS (Complex I-V) protein expression, markers of mitochondrial content (p < 0.05). Multiple comparisons showed that total OXPHOS protein expression in β-GPA + exercised leg (+61.8% vs placebo + rested leg) was significantly higher than in exercised leg (+33.0% vs placebo + rested leg) (p < 0.05). Main effects of training and β-GPA were observed in muscle wet weight (p < 0.05). The % change in muscle mass with resistance training was significantly lower in β-GPA group (+3.92%) than in placebo group (+9.92%) (p < 0.05).
The study suggests that β-GPA, a creatine inhibitor, enhances resistance training-induced mitochondrial biogenesis. Furthermore, β-GPA can attenuate, but not completely abolish, resistance training-induced gains in muscle mass.