Barbara M Crisol1, Camilla B Veiga2, Renata R Braga1, Luciene Lenhare1,3, Igor L Baptista4, Rafael C Gaspar1, Vitor R Muñoz1, André V Cordeiro1, Adelino S R da Silva5,6, Dennys E Cintra2, Leandro P Moura1,7, José R Pauli1,7, Eduardo R Ropelle8,9,10. 1. Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Pedro Zaccaria, 1300, Limeira, SP, 13484-350, Brazil. 2. Laboratory of Nutritional Genomics (LabGeN), School of Applied Sciences, University of Campinas, Limeira, SP, Brazil. 3. Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil. 4. Laboratory of Cell and Tissue Biology, School of Applied Sciences, University of Campinas, Limeira, SP, Brazil. 5. Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto, SP, Brazil. 6. Medical School, and Postgraduate Program in Physical Education and Sport, School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil. 7. CEPECE-Center of Research in Sport Sciences, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, Brazil. 8. Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Pedro Zaccaria, 1300, Limeira, SP, 13484-350, Brazil. eduardoropelle@gmail.com. 9. Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil. eduardoropelle@gmail.com. 10. CEPECE-Center of Research in Sport Sciences, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, Brazil. eduardoropelle@gmail.com.
Abstract
PURPOSE: Nicotinamide riboside (NR) acts as a potent NAD+ precursor and improves mitochondrial oxidative capacity and mitochondrial biogenesis in several organisms. However, the effects of NR supplementation on aerobic performance remain unclear. Here, we evaluated the effects of NR supplementation on the muscle metabolism and aerobic capacity of sedentary and trained mice. METHODS: Male C57BL/6 J mice were supplemented with NR (400 mg/Kg/day) over 5 and 10 weeks. The training protocol consisted of 5 weeks of treadmill aerobic exercise, for 60 min a day, 5 days a week. Bioinformatic and physiological assays were combined with biochemical and molecular assays to evaluate the experimental groups. RESULTS: NR supplementation by itself did not change the aerobic performance, even though 5 weeks of NR supplementation increased NAD+ levels in the skeletal muscle. However, combining NR supplementation and aerobic training increased the aerobic performance compared to the trained group. This was accompanied by an increased protein content of NMNAT3, the rate-limiting enzyme for NAD + biosynthesis and mitochondrial proteins, including MTCO1 and ATP5a. Interestingly, the transcriptomic analysis using a large panel of isogenic strains of BXD mice confirmed that the Nmnat3 gene in the skeletal muscle is correlated with several mitochondrial markers and with different phenotypes related to physical exercise. Finally, NR supplementation during aerobic training markedly increased the amount of type I fibers in the skeletal muscle. CONCLUSION: Taken together, our results indicate that NR may be an interesting strategy to improve mitochondrial metabolism and aerobic capacity.
PURPOSE:Nicotinamide riboside (NR) acts as a potent NAD+ precursor and improves mitochondrial oxidative capacity and mitochondrial biogenesis in several organisms. However, the effects of NR supplementation on aerobic performance remain unclear. Here, we evaluated the effects of NR supplementation on the muscle metabolism and aerobic capacity of sedentary and trained mice. METHODS: Male C57BL/6 J mice were supplemented with NR (400 mg/Kg/day) over 5 and 10 weeks. The training protocol consisted of 5 weeks of treadmill aerobic exercise, for 60 min a day, 5 days a week. Bioinformatic and physiological assays were combined with biochemical and molecular assays to evaluate the experimental groups. RESULTS: NR supplementation by itself did not change the aerobic performance, even though 5 weeks of NR supplementation increased NAD+ levels in the skeletal muscle. However, combining NR supplementation and aerobic training increased the aerobic performance compared to the trained group. This was accompanied by an increased protein content of NMNAT3, the rate-limiting enzyme for NAD + biosynthesis and mitochondrial proteins, including MTCO1 and ATP5a. Interestingly, the transcriptomic analysis using a large panel of isogenic strains of BXD mice confirmed that the Nmnat3 gene in the skeletal muscle is correlated with several mitochondrial markers and with different phenotypes related to physical exercise. Finally, NR supplementation during aerobic training markedly increased the amount of type I fibers in the skeletal muscle. CONCLUSION: Taken together, our results indicate that NR may be an interesting strategy to improve mitochondrial metabolism and aerobic capacity.
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