Nitrate-induced improvements in exercise performance are coincident with exuberant changes in metabolic genes and the metabolome in zebrafish skeletal muscle.

2021 ◽  
Author(s):  
Rosa Moon Keller ◽  
Laura M. Beaver ◽  
Patrick N. Reardon ◽  
Mary C. Prater ◽  
Lisa Truong ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Test ◽  
Exercise Performance ◽  
Nutrient Sensing ◽  
Strenuous Exercise ◽  
Oxygen Cost ◽  
Skeletal Muscle Function ◽  
Zebrafish Model ◽  
Nitrate Treatment ◽  
Nitrate Concentrations

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 10-5), creatine (P =6.0 x 10-7), ATP (P = 2.0 x 10-6), 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.

scholarly journals Nitrate-Induced Improvements in Exercise Performance Is Coincident With Exuberant Changes in Metabolic Genes and the Metabolome in Zebrafish (Danio rerio) Skeletal Muscle

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1292-1292
Author(s):  
Rosa Keller ◽  
Laura Beaver ◽  
Patrick Reardon ◽  
Jan Stevens ◽  
Norman Hord
Keyword(s):  
Skeletal Muscle ◽  
Exercise Performance ◽  
Tricarboxylic Acid Cycle ◽  
Quantitative Polymerase Chain Reaction ◽  
Nutrient Sensing ◽  
Strenuous Exercise ◽  
Control Fish ◽  
Resonance Spectroscopy ◽  
Oxygen Cost ◽  
Nitrate Treatment

Abstract Objectives Dietary nitrate (NO3−) supplementation improves exercise performance by reducing the oxygen cost of exercise and enhancing skeletal muscle function. However, the mechanisms underlying the beneficial effects on exercise performance are not well understood and may be supported by changes in metabolism within the skeletal muscle. The purpose of this study was to elucidate nitrate-induced changes in skeletal muscle energy metabolism associated with improvements in exercise performance that may reflect enhanced metabolic flexibility. Methods Fish were exposed to sodium nitrate (60.7 mg/L, 303.5 mg/L, and 606.9 mg/L), or control water, for 21 days and analyzed at intervals during a strenuous exercise test. Nitrate storage in muscle was measured using chemiluminescence. We utilized nuclear magnetic resonance spectroscopy (NMR), liquid-chromatography tandem mass spectrometry (LC-MS/MS) untargeted metabolomics and real-time quantitative polymerase chain reaction (RT-qPCR) to determine changes in muscle metabolism with nitrate and exercise. Results Nitrate treatment significantly increased muscle nitrate concentrations, while muscle nitrate levels declined with increasing exercise duration, and nitrate treatment was associated with a decrease in the oxygen cost of exercise. In skeletal muscle, nitrate treatment upregulated expression of genes central to nutrient sensing (mtor), glucose (hk2) and lipid metabolism (acaca), redox signaling (nrf2a) and muscle differentiation (sox6). Nitrate treatment caused rested skeletal muscle to have significantly increased metabolites directly linked to energy production (phosphocreatine (PCr), creatine (Cr), adenosine nucleosides, purines, glycolytic, fatty acid and tricarboxylic acid cycle (TCA) intermediates) and a concomitant decrease in these metabolites after exercise, compared to rested-control fish. Conclusions Our data suggest that nitrate exposure may improve exercise performance by changing the metabolic programming of muscle prior to exercise, thus increasing the availability of energy producing metabolites required for exercise such as ATP and phosphocreatine. Funding Sources Celia Strickland and G. Kenneth Austin III Endowment and National Institutes of Health.

scholarly journals Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

2021 ◽  
Author(s):  
Daniel J Ham ◽  
Anastasiya Boersch ◽  
Kathrin Chojnowska ◽  
Shuo Lin ◽  
Aurel B Leuchtmann ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Calorie Restriction ◽  
Expression Profiles ◽  
Life Quality ◽  
Gene Expression Profiles ◽  
Nutrient Sensing ◽  
Skeletal Muscle Function ◽  
Muscle Gene Expression ◽  
Muscle Aging ◽  
Age Related

As global life expectancy continues to climb, maintaining skeletal muscle function is increasingly essential to ensure a good life quality for aging populations. Calorie restriction (CR) is the most potent and reproducible intervention to extend health and lifespan, but is largely unachievable in humans. Therefore, identification of 'CR mimetics' has received much attention. CR targets nutrient-sensing pathways centering on mTORC1. The mTORC1 inhibitor, rapamycin, has been proposed as a potential CR mimetic and is proven to counteract age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow muscle aging. Contrary to our expectation, long-term CR and rapamycin-treated geriatric mice display distinct skeletal muscle gene expression profiles despite both conferring benefits to aging skeletal muscle. Furthermore, CR improved muscle integrity in a mouse with nutrient-insensitive sustained muscle mTORC1 activity and rapamycin provided additive benefits to CR in aging mouse muscles. Therefore, RM and CR exert distinct, compounding effects in aging skeletal muscle, opening the possibility of parallel interventions to counteract muscle aging.

scholarly journals Nitrate and Nitrite Treatment Modulate Performance and Available Fuel Sources In Zebrafish Muscle and Liver

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1758-1758
Author(s):  
Rosa Keller ◽  
Laura Beaver ◽  
Patrick Reardon ◽  
Norman Hord
Keyword(s):  
Skeletal Muscle ◽  
Exercise Performance ◽  
Creatine Phosphate ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Muscle Gene Expression ◽  
Nitrate Treatment ◽  
Muscle Gene ◽  
Nitrate And Nitrite

Abstract Objectives Treatment with nitrate, but not nitrite, improves exercise performance but the mechanisms responsible are not fully understood. Thus, we tested the hypothesis that nitrate and nitrite treatment alter exercise performance through regulation of genes related to glucose and lipid metabolism in skeletal muscle and liver. Furthermore, we tested the hypothesis that nitrate treatment caused increased abundance and utilization of metabolic fuels in muscle that require less oxygen for energy production. Methods Adult zebrafish fish were exposed to sodium nitrate (606.9 mg NaNO3/L water), sodium nitrite (19.5 mg NaNO2/L of water), or control water for 21 days (n = 9–12/treatment). Liver and muscle gene expression were analyzed by quantitative real-time PCR and liver and muscle metabolomes were assessed by 1H-NMR untargeted metabolomics. Results Nitrite treatment significantly increased carnitine palmitoyl transferase 1b (cpt1b) expression in the liver and significantly decreased acetyl-CoA carboxylase (acaca) expression in skeletal muscle. Nitrate treatment significantly increased expression of peroxisome proliferator activated receptor-γ (pparg) muscle while acaca significantly decreased in skeletal muscle. Nitrate treatment also induced significant increases in metabolic fuels, such as ATP and creatine phosphate, and fuel sources including β-hydroxybutyrate and glycolytic intermediates in rested skeletal muscle. After a graded exercise test, these metabolites decreased in skeletal muscle of nitrate-treated fish while they increased with exercise in the skeletal muscle of control-treated zebrafish. Conclusions Our data are consistent with the hypothesis that nitrate treatment altered lipid and carbohydrate metabolism of zebrafish, in part, through a pparg mediated mechanism in the liver, and may improve exercise performance through utilization of fuel sources that require less oxygen during exercise. In contrast, our data indicate that nitrite may attenuate exercise performance, in part, by promoting dependence on fatty acid oxidation in the liver of zebrafish. These mechanisms may mediate improved exercise tolerance in populations with cardiovascular disease. Funding Sources Celia Strickland and G. Kenneth Austin III Endowment and National Institutes of Health.

scholarly journals Recent Advance on Vitamin D in Athletes

2021 ◽  
Vol 30 (3) ◽  
pp. 278-287
Author(s):  
Jinkyung Cho ◽  
Soo-Hyun Park ◽  
Hong-Sun Song
Keyword(s):  
Skeletal Muscle ◽  
Vitamin D ◽  
Exercise Performance ◽  
Muscle Function ◽  
Vitamin D Supplementation ◽  
Molecular Pathways ◽  
Skeletal Muscle Function ◽  
Vitamin D Receptors ◽  
Beneficial Effects ◽  
Myocyte Proliferation

PURPOSE: Vitamin D plays important roles in calcium homeostasis and bone metabolism. Since vitamin D receptors (VDRs) are located in a variety of organs, including skeletal muscle, vitamin D has potentially widespread effects. The purpose of this review was to summarize the current understanding of the effects of vitamin D on muscle function and exercise performance in athletes.METHODS: In this narrative review, we summarized previous studies by searching the literature in the PubMed, Google Scholar, and Science Direct databases.RESULTS: Vitamin D has been shown to regulate multiple actions in skeletal muscle tissue, such as myocyte proliferation and growth via genomic and non-genomic molecular pathways. Higher levels of vitamin D are associated with improved skeletal muscle function and exercise performance. Moreover, in some studies, vitamin D supplementation has beneficial effects on muscle strength in athletes, especially those who are vitamin D-deficient.CONCLUSIONS: Vitamin D appears to have beneficial effects on muscle and exercise performance in athletes. However, more studies are needed to clarify the action and dosage of vitamin D in athletes.

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