Triple-Isotope Tracing for Pathway Discernment of NMN-Induced NAD+ Biosynthesis in Whole Mice.

TitleTriple-Isotope Tracing for Pathway Discernment of NMN-Induced NAD+ Biosynthesis in Whole Mice.
Publication TypeJournal Article
Year of Publication2023
AuthorsSauve AA, Wang Q, Zhang N, Kang S, Rathmann A, Yang Y
JournalInt J Mol Sci
Volume24
Issue13
Date Published2023 Jul 05
ISSN1422-0067
KeywordsAging, 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.

DOI10.3390/ijms241311114
Alternate JournalInt J Mol Sci
PubMed ID37446292
PubMed Central IDPMC10342116
Grant List9R01AG066192-07 / AG / NIA NIH HHS / United States