Altered acute metabolic response to muscle stimulation in muscular dystrophic mice observed by phosphorus-31 magnetic resonance spectroscopy and fingerprinting

Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration. Impaired muscle metabolism has been implicated in DMD, and interventions aimed at normalizing and enhancing metabolic function, such as exercise, have been proposed as potential therapeutic strategies. However, the metabolic response to exercise in DMD remains incompletely understood. This study aimed to investigate the acute metabolic response to muscle stimulation mimicking high-intensity exercise. Using phosphorus-31 magnetic resonance spectroscopy (³¹P-MRS) and fingerprinting (³¹P-MRSF), changes in phosphocreatine (PCr) recovery rate and creatine kinase (CK) shuttle activity following repeated muscle stimulation were quantified in mdx mice, a well-established mouse model of DMD. The impact of muscle degeneration and aging was assessed by comparing mdx and control mice in two age groups: young (10-12 wk) and adult (20-22 wk). Young control mice exhibited a significant increase in PCr recovery rate and CK rate constant following muscle stimulation, indicating a positive acute metabolic adaptation. In contrast, mdx mice showed no increase in PCr recovery rate and an attenuated increase in CK rate constant, suggesting compromised mitochondrial function and CK shuttle efficiency. These findings indicate that muscle degeneration in DMD impairs acute metabolic response to high-intensity muscle contractions, potentially limiting exercise-induced metabolic benefits. Furthermore, this study demonstrates the utility of ³¹P-MRS and ³¹P-MRSF as noninvasive tools to assess muscle metabolism and exercise response in vivo.<b>NEW & NOTEWORTHY</b> The results of the current study demonstrate the impact of muscle degeneration and aging on exercise-induced metabolic response. The absence of an increase in phosphocreatine recovery rate and the attenuated increase in creatine kinase shuttle activity observed in mdx mice suggest impaired acute metabolic adaptation to high-intensity exercise. These findings underscore the potential of phosphorus-31 magnetic resonance spectroscopy and fingerprinting for noninvasive assessment of muscle bioenergetics in vivo.