Title | Triple-Isotope Tracing for Pathway Discernment of NMN-Induced NAD+ Biosynthesis in Whole Mice. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Sauve AA, Wang Q, Zhang N, Kang S, Rathmann A, Yang Y |
Journal | Int J Mol Sci |
Volume | 24 |
Issue | 13 |
Date Published | 2023 Jul 05 |
ISSN | 1422-0067 |
Keywords | Aging, Animals, Biological Transport, Humans, Mice, NAD, Nicotinamide Mononucleotide |
Abstract | Numerous efforts in basic and clinical studies have explored the potential anti-aging and health-promoting effects of NAD+-boosting compounds such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Despite these extensive efforts, our understanding and characterization of their whole-body pharmacodynamics, impact on NAD+ tissue distribution, and mechanism of action in various tissues remain incomplete. In this study, we administered NMN via intraperitoneal injection or oral gavage and conducted a rigorous evaluation of NMN's pharmacodynamic effects on whole-body NAD+ homeostasis in mice. To provide more confident insights into NMN metabolism and NAD+ biosynthesis across different tissues and organs, we employed a novel approach using triple-isotopically labeled [18O-phosphoryl-18O-carbonyl-13C-1-ribosyl] NMN. Our results provide a more comprehensive characterization of the NMN impact on NAD+ concentrations and absolute amounts in various tissues and the whole body. We also demonstrate that mice primarily rely on the nicotinamide and NR salvage pathways to generate NAD+ from NMN, while the uptake of intact NMN plays a minimal role. Overall, the tissue-specific pharmacodynamic effects of NMN administration through different routes offer novel insights into whole-body NAD+ homeostasis, laying a crucial foundation for the development of NMN as a therapeutic supplement in humans. |
DOI | 10.3390/ijms241311114 |
Alternate Journal | Int J Mol Sci |
PubMed ID | 37446292 |
PubMed Central ID | PMC10342116 |
Grant List | 9R01AG066192-07 / AG / NIA NIH HHS / United States |