NAD+ precursor increases aerobic performance in mice
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.
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.
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.
Taken together, our results indicate that NR may be an interesting strategy to improve mitochondrial metabolism and aerobic capacity.
KeywordsNicotinamide riboside Exercise Training Mitochondrial markers Skeletal muscle Fiber type
This work was supported by grants from the São Paulo Research Foundation (FAPESP–2016/05499-1, 2016/01089-3, and 2018/07634-9) and was financed in part by the National Council for Scientific and Technological Development (CNPq) (case numbers 304771/2017-1 and 401189/2016-3) and the Coordination for the Improvement of Higher Education Personnel (CAPES)–Brazil–Finance Code 001.
BMC performed all the experiments and prepared the figures. BMC and CBV performed the diet production, animal experiments, tissue extraction, and Western blotting analyses. RRB performed the diet production, animal experiments, tissue extraction, and sample preparation. BMC and LL performed the Western blotting analyses. ILB and BMC performed the fiber type experiments. BMC, RCG, VRM, and AVC performed the performance test, exercise training, and tissue extraction. BMC performed the NAD+ quantification and mRNA analyses. ERR performed the bioinformatics analysis. LPM, ASRS, DEC, and JRP provided the laboratory support, discussion, and reviewed the manuscript. BMC and ERR wrote the manuscript. ERR was responsible for the financial support.
Compliance with ethical standards
Conflict of interests
There is no conflict of interest involving the authors and the results presented in this study.
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