Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion.

Yamamoto T, Byun J, Zhai P, Ikeda Y, Oka S, Sadoshima J

PloS one6 Jun 2014Cited by 252 (Europe PMC)

PMID24905194PMCIDPMC4048236DOI10.1371/journal.pone.0098972PepBankPUB-24905194

Summary

Nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme for nicotinamide adenine dinucleotide (NAD+) synthesis, and Sirt1, an NAD+-dependent histone deacetylase, protect the heart against ischemia/reperfusion (I/R). It remains unknown whether Nampt mediates the protective effect of ischemic preconditioning (IPC), whether nicotinamide mononucleotide (NMN, 500 mg/kg), a product of Nampt in the NAD+ salvage pathway, mimics the effect of IPC, or whether caloric restriction (CR) upregulates Nampt and protects the heart through a Sirt1-dependent mechanism. IPC upregulated Nampt protein, and the protective effect of IPC against ischemia (30 minutes) and reperfusion (24 hours) was attenuated at both early and late phases in Nampt +/- mice, suggesting that Nampt plays an essential role in mediating the protective effect of IPC. In order to mimic the effect of Nampt, NMN was administered by intraperitoneal injection. NMN significantly increased the level of NAD+ in the heart at baseline and prevented a decrease in NAD+ during ischemia. NMN protected the heart from I/R injury when it was applied once 30 minutes before ischemia or 4 times just before and during reperfusion, suggesting that exogenous NMN protects the heart from I/R injury in both ischemic and reperfusion phases. The protective effect of NMN was accompanied by decreases in acetylation of FoxO1, but it was not obvious in Sirt1 KO mice, suggesting that the effect of NMN is mediated through activation of Sirt1. Compared to control diet (90% calories), CR (60% calories for 6 weeks) in mice led to a significant reduction in I/R injury, accompanied by upregulation of Nampt. The protective effect of CR against I/R injury was not significant in cardiac-specific Sirt1 KO mice, suggesting that the protective effect of CR is in part mediated through the Nampt-Sirt1 pathway. In conclusion, exogenous application of NMN and CR protects the heart by both mimicking IPC and activating Sirt1.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Mechanism
In mice, NMN significantly increased cardiac NAD at baseline.
In plain wordsIn mice, NMN increased heart NAD levels before ischemia.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseCardiac NAD at baseline
Study
mousen: not reported in source
myocardial ischemia/reperfusion
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
500 mg/kg · intraperitonealAs given in this study (mouse).
Source sentences
Summary
NMN significantly increased the level of NAD+ in the heart at baseline and prevented a decrease in NAD+ during ischemia.
1 context sentence(design, population, supporting numbers)
Summary · context
In order to mimic the effect of Nampt, NMN was administered by intraperitoneal injection.
Show in the study text Report a problemFND-2490519401
02AnimalAnimal study (in vivo)Mechanism
In mice, NMN prevented a decrease in cardiac NAD during ischemia.
In plain wordsIn mice, NMN prevented heart NAD levels from decreasing during ischemia.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseCardiac NAD during ischemia
Study
mousen: not reported in source
myocardial ischemia/reperfusion
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
500 mg/kg · intraperitonealAs given in this study (mouse).
Source sentences
Summary
NMN significantly increased the level of NAD+ in the heart at baseline and prevented a decrease in NAD+ during ischemia.
1 context sentence(design, population, supporting numbers)
Summary · context
In order to mimic the effect of Nampt, NMN was administered by intraperitoneal injection.
Show in the study text Report a problemFND-2490519402
03AnimalAnimal study (in vivo)Efficacy outcome
In mice, NMN given once before ischemia protected the heart against ischemia/reperfusion injury.
In plain wordsIn mice, NMN given once before ischemia protected the heart from ischemia/reperfusion injury.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseIschemia/reperfusion injury with pre-ischemic NMN
Study
mousen: not reported in source
myocardial ischemia/reperfusion
Outcome group
Heart function · Cardiovascular
Studied dose
500 mg/kg · intraperitonealAs given in this study (mouse).
Source sentences
Summary
NMN protected the heart from I/R injury when it was applied once 30 minutes before ischemia or 4 times just before and during reperfusion, suggesting that exogenous NMN protects the heart from I/R injury in both ischemic and reperfusion phases.
1 context sentence(design, population, supporting numbers)
Summary · context
In order to mimic the effect of Nampt, NMN was administered by intraperitoneal injection.
Show in the study text Report a problemFND-2490519403
04AnimalAnimal study (in vivo)Efficacy outcome
In mice, NMN given four times just before and during reperfusion protected the heart against ischemia/reperfusion injury.
In plain wordsIn mice, NMN given repeatedly just before and during reperfusion protected the heart from ischemia/reperfusion injury.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseIschemia/reperfusion injury with reperfusion NMN
Study
mousen: not reported in source
myocardial ischemia/reperfusion
Outcome group
Heart function · Cardiovascular
Studied dose
500 mg/kg · intraperitonealAs given in this study (mouse).
Source sentences
Summary
NMN protected the heart from I/R injury when it was applied once 30 minutes before ischemia or 4 times just before and during reperfusion, suggesting that exogenous NMN protects the heart from I/R injury in both ischemic and reperfusion phases.
1 context sentence(design, population, supporting numbers)
Summary · context
In order to mimic the effect of Nampt, NMN was administered by intraperitoneal injection.
Show in the study text Report a problemFND-2490519404
05AnimalAnimal study (in vivo)Mechanism
In mice, the protective effect of NMN accompanied decreased FoxO1 acetylation.
In plain wordsIn mice, NMN's heart protection accompanied reduced FoxO1 acetylation.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseFoxO1 acetylation
Study
mousen: not reported in source
myocardial ischemia/reperfusion
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
500 mg/kg · intraperitonealAs given in this study (mouse).
Source sentences
Summary
The protective effect of NMN was accompanied by decreases in acetylation of FoxO1, but it was not obvious in Sirt1 KO mice, suggesting that the effect of NMN is mediated through activation of Sirt1.
1 context sentence(design, population, supporting numbers)
Summary · context
In order to mimic the effect of Nampt, NMN was administered by intraperitoneal injection.
Show in the study text Report a problemFND-2490519405
06AnimalAnimal study (in vivo)Efficacy outcome
In Sirt1 knockout mice, the protective effect of administered NMN was not obvious.
In plain wordsIn mice lacking Sirt1, NMN's protective effect on the heart was not obvious.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
Direction not reportedCardiac protection in Sirt1 knockout mice
Study
mousen: not reported in source
Sirt1 knockout mice with myocardial ischemia/reperfusion
Outcome group
Heart function · Cardiovascular
Studied dose
500 mg/kg · intraperitonealAs given in this study (mouse).
Source sentences
Summary
The protective effect of NMN was accompanied by decreases in acetylation of FoxO1, but it was not obvious in Sirt1 KO mice, suggesting that the effect of NMN is mediated through activation of Sirt1.
1 context sentence(design, population, supporting numbers)
Summary · context
In order to mimic the effect of Nampt, NMN was administered by intraperitoneal injection.
Show in the study text Report a problemFND-2490519406

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

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