Publication:
Reduced nicotinamide mononucleotide is a new and potent NAD+ precursor in mammalian cells and mice

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dc.contributor.authorZapata- Pérez, Rubén
dc.contributor.authorTammaro, Alessandra
dc.contributor.authorSchomakers, Bauke V.
dc.contributor.authorScantlebery, Angelique M. L.
dc.contributor.authorDenis, Simone
dc.contributor.authorElfrink, Hyung L.
dc.contributor.authorGiroud- Gerbetant, Judith
dc.contributor.authorCantó, Carles
dc.contributor.authorLópez Leonardo, Carmen
dc.contributor.authorMcIntyre, Rebecca L.
dc.contributor.authorWeeghel, Michel van
dc.contributor.authorSánchez Ferrer, Álvaro
dc.contributor.authorHoutkooper, Riekelt H.
dc.contributor.departmentQuímica Orgánica
dc.contributor.departmentBioquímica y Biología Molecular A
dc.contributor.otherFacultad de Química
dc.contributor.otherFacultad de Veterinaria
dc.date.accessioned2025-12-17T08:16:12Z
dc.date.available2025-12-17T08:16:12Z
dc.date.copyright© 2021 The Authors
dc.date.issued2021-03-16
dc.description.abstractNicotinamide adenine dinucleotide (NAD+) homeostasis is constantly compromised due to degradation by NAD+-dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.
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dc.format.extent17
dc.identifier.citationThe FASEB Journal. 2021;35:e21456
dc.identifier.doihttps://doi.org/10.1096/fj.202001826R
dc.identifier.eissn1530-6860
dc.identifier.issn0892-6638
dc.identifier.urihttp://hdl.handle.net/10201/180749
dc.languageeng
dc.publisherWiley
dc.relationThe authors would like to thank Loes Butter for assistance with hypoxia/reoxygenation assays. AT is financially supported by the NWO-FAPESP joint grant on healthy ageing, executed by ZonMw (no. 457002002). RZP is supported by a postdoctoral grant from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement number 840110. Work in the Houtkooper group is financially supported by an ERC Starting grant (no. 638290), a VIDI grant from ZonMw (no. 91715305), and a grant from the Velux Stiftung (no. 1063). ASF group is supported by Spanish grants from MINECO-FEDER (BIO2013-45336- R) and from Ayudas a los Grupos y Unidades de Excelencia Científica de la Región de Murcia, Fundación Séneca-Agencia de Ciencia y Tecnología de la Región de Murcia (19893/GERM/15, Programa de Apoyo a la Investigación 2014).
dc.relation.publisherversionhttps://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202001826R
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectMetabolism
dc.subjectNAD+
dc.subjectNMNH
dc.subjectNicotinamide mononucleotide
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleReduced nicotinamide mononucleotide is a new and potent NAD+ precursor in mammalian cells and mice
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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relation.isAuthorOfPublication434dc353-54ab-4dcc-b277-61e489ca79d6
relation.isAuthorOfPublicationaa6ca3f7-ee95-4c3b-b93d-82bbb7c57dd3
relation.isAuthorOfPublication.latestForDiscovery434dc353-54ab-4dcc-b277-61e489ca79d6
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