Publication: Reduced nicotinamide mononucleotide is a new and potent NAD+ precursor in mammalian cells and mice
Authors
Zapata- Pérez, Rubén ; Tammaro, Alessandra ; Schomakers, Bauke V. ; Scantlebery, Angelique M. L. ; Denis, Simone ; Elfrink, Hyung L. ; Giroud- Gerbetant, Judith ; Cantó, Carles ; López Leonardo, Carmen ; McIntyre, Rebecca L. ; Weeghel, Michel van ; Sánchez Ferrer, Álvaro ; Houtkooper, Riekelt H.
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Facultad de Química ; Facultad de Veterinaria
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Publisher
Wiley
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DOI
https://doi.org/10.1096/fj.202001826R
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info:eu-repo/semantics/article
Description
Abstract
Nicotinamide 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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Citation
The FASEB Journal. 2021;35:e21456
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/