TitleNitrate-induced improvements in exercise performance are coincident with exuberant changes in metabolic genes and the metabolome in zebrafish skeletal muscle.
Publication TypeJournal Article
Year of Publication2021
AuthorsKeller, RMoon, Beaver, LM, Reardon, PN, Prater, MC, Truong, L, Robinson, MM, Tanguay, RL, Stevens, JFred, Hord, NG
JournalJ Appl Physiol (1985)
Date Published05/2021

Dietary nitrate supplementation improves exercise performance by reducing the oxygen cost of exercise and enhancing skeletal muscle function. However, the mechanisms underlying these effects are not well understood. The purpose of this study was to assess changes in skeletal muscle energy metabolism associated with exercise performance in a zebrafish model. Fish were exposed to sodium nitrate (60.7 mg/L, 303.5 mg/L, 606.9 mg/L), or control water, for 21 days and analyzed at intervals (5, 10, 20, 30, 40 cm/sec) during a two-hour strenuous exercise test. We measured oxygen consumption during an exercise test and assessed muscle nitrate concentrations, gene expression and the muscle metabolome before, during and after exercise. Nitrate exposure reduced the oxygen cost of exercise and increased muscle nitrate concentrations at rest, which were reduced with increasing exercise duration. In skeletal muscle, nitrate treatment upregulated expression of genes central to nutrient sensing (mtor), redox signaling (nrf2a) and muscle differentiation (sox6). In rested muscle, nitrate treatment increased phosphocreatine (P = 0.002), creatine (P =0.0005), ATP (P = 0.0008), ADP (P = 0.002), and AMP (P =0.004) compared to rested-control muscle. Following the highest swimming speed, concentration of phosphocreatine (P = 8.0 x 10), creatine (P =6.0 x 10), ATP (P = 2.0 x 10), ADP (P = 0.0002), and AMP (P =0.004) decreased compared to rested nitrate muscle. Our data suggests nitrate exposure in zebrafish lowers the oxygen cost of exercise by changing the metabolic programming of muscle prior to exercise and increasing availability of energy-rich metabolites required for exercise.

Alternate JournalJ Appl Physiol (1985)
PubMed ID34043471