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Reduced nicotinamide mononucleotide is a new and potent NAD + precursor in mammalian cells and mice
Author(s) -
ZapataPérez Rubén,
Tammaro Alessandra,
Schomakers Bauke V.,
Scantlebery Angelique M. L.,
Denis Simone,
Elfrink Hyung L.,
GiroudGerbetant Judith,
Cantó Carles,
LópezLeonardo Carmen,
McIntyre Rebecca L.,
van Weeghel Michel,
SánchezFerrer Álvaro,
Houtkooper Riekelt H.
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202001826r
Subject(s) - nad+ kinase , nicotinamide mononucleotide , nicotinamide adenine dinucleotide , nicotinamide , nicotinamide phosphoribosyltransferase , chemistry , biochemistry , niacinamide , enzyme
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.