Nicotinamide mononucleotide attenuates HIF-1α activation and fibrosis in hypoxic adipose tissue via NAD⁺/SIRT1 axis.

Wu K, Li B, Ma Y, Tu T, Lin Q, Zhu J, Zhou Y, Liu N, Liu Q

Frontiers in endocrinology26 Jan 2023Cited by 12 (Europe PMC)

PMID36777361PMCIDPMC9909340DOI10.3389/fendo.2023.1099134PepBankPUB-36777361

Summary

BackgroundFibrosis is increasingly considered as a major contributor in adipose tissue dysfunction. Hypoxic activation of hypoxia-inducible factor 1α (HIF-1α) induces a profibrotic transcription, leading to adipose fibrosis. Nicotinamide mononucleotide (NMN), a member of the vitamin B₃ family, has been shown to relieve hepatic and cardiac fibrosis, but its effects on hypoxic adipose fibrosis and the underlying mechanism remain unclear. We aimed to elucidate the roles of NMN in regulating HIF-1α and fibrosis in hypoxic adipose tissue.MethodsMice were placed in a hypobaric chamber for four weeks to induce adipose fibrosis. NMN (500 mg/kg, every three days) was administered by intraperitoneal injection. In vitro, Stromal vascular fractions (SVF) cells were treated by hypoxia with or without NMN (200μM), sirtinol (25μM, a SIRT1 inhibitor) and CoCl₂ (100μM, a HIF1α enhancer). The effects of NMN on hypoxia-associated adipose fibrosis, inflammation, NAD⁺/SIRT1 axis alteration, and HIF-1α activation were evaluated by real-time polymerase chain reaction (PCR), western blots, immunohistochemistry staining, immunoprecipitation, and assay kits.ResultsMice placed in a hypoxic chamber for four weeks showed obvious adipose fibrosis and inflammation, which were attenuated by NMN. NMN also restore the compromised NAD⁺/SIRT1 axis and inhibited the activation of HIF-1α induced by hypoxia. In hypoxia-induced SVFs, the SIRT1 inhibitor sirtinol blocked the anti-fibrotic and anti-inflammatory effects of NMN, upregulated the HIF-1α and its acetylation level. The HIF1α stabilizer CoCl₂ showed similar effects as sirtinol.ConclusionNMN effectively attenuated HIF-1α activation-induced adipose fibrosis and inflammation by restoring the compromised NAD⁺/SIRT1 axis.

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

Results from this study9

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

01AnimalAnimal study (in vivo)Efficacy outcome
In hypoxic mice, NMN attenuated adipose fibrosis.
In plain wordsIn mice exposed to hypoxia, NMN reduced adipose fibrosis.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseAdipose fibrosis
Study
mousen: not reported in source
hypoxia-induced adipose fibrosis
Outcome group
Organ injury · Metabolic and weight
Studied dose
500 mg/kg every three days · intraperitoneal injectionAs given in this study (mouse).
Source sentences
Summary
Mice placed in a hypoxic chamber for four weeks showed obvious adipose fibrosis and inflammation, which were attenuated by NMN.
1 context sentence(design, population, supporting numbers)
Summary · context
Mice were placed in a hypobaric chamber for four weeks to induce adipose fibrosis. NMN (500 mg/kg, every three days) was administered by intraperitoneal injection.
Show in the study text Report a problemFND-3677736101
02AnimalAnimal study (in vivo)Efficacy outcome
In hypoxic mice, NMN attenuated adipose inflammation.
In plain wordsIn mice exposed to hypoxia, NMN reduced adipose inflammation.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseAdipose inflammation
Study
mousen: not reported in source
hypoxia-induced adipose fibrosis
Outcome group
Inflammation markers · Metabolic and weight
Studied dose
500 mg/kg every three days · intraperitoneal injectionAs given in this study (mouse).
Source sentences
Summary
Mice placed in a hypoxic chamber for four weeks showed obvious adipose fibrosis and inflammation, which were attenuated by NMN.
1 context sentence(design, population, supporting numbers)
Summary · context
Mice were placed in a hypobaric chamber for four weeks to induce adipose fibrosis. NMN (500 mg/kg, every three days) was administered by intraperitoneal injection.
Show in the study text Report a problemFND-3677736102
03AnimalAnimal study (in vivo)Mechanism
In hypoxic mice, NMN restored the compromised NAD/SIRT1 axis.
In plain wordsIn mice exposed to hypoxia, NMN restored the impaired NAD/SIRT1 pathway.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseNAD/SIRT1 axis
Study
mousen: not reported in source
hypoxia-induced adipose fibrosis
Outcome group
Receptor activity and mechanism · Metabolic and weight
Studied dose
500 mg/kg every three days · intraperitoneal injectionAs given in this study (mouse).
Source sentences
Summary
NMN also restore the compromised NAD⁺/SIRT1 axis and inhibited the activation of HIF-1α induced by hypoxia.
1 context sentence(design, population, supporting numbers)
Summary · context
Mice were placed in a hypobaric chamber for four weeks to induce adipose fibrosis. NMN (500 mg/kg, every three days) was administered by intraperitoneal injection.
Show in the study text Report a problemFND-3677736103
04AnimalAnimal study (in vivo)Mechanism
In hypoxic mice, NMN inhibited hypoxia-induced HIF-1α activation.
In plain wordsIn mice exposed to hypoxia, NMN reduced HIF-1α activation.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseHIF-1α activation
Study
mousen: not reported in source
hypoxia-induced adipose fibrosis
Outcome group
Receptor activity and mechanism · Metabolic and weight
Studied dose
500 mg/kg every three days · intraperitoneal injectionAs given in this study (mouse).
Source sentences
Summary
NMN also restore the compromised NAD⁺/SIRT1 axis and inhibited the activation of HIF-1α induced by hypoxia.
1 context sentence(design, population, supporting numbers)
Summary · context
Mice were placed in a hypobaric chamber for four weeks to induce adipose fibrosis. NMN (500 mg/kg, every three days) was administered by intraperitoneal injection.
Show in the study text Report a problemFND-3677736104

Studies that did not test the peptide alone5

In this study, NMN (nicotinamide mononucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking NMN (nicotinamide mononucleotide).

05LabNot a test of NMN (nicotinamide mononucleotide) aloneIn vitro (cells)Mechanism
In hypoxic SVF cells, sirtinol blocked the antifibrotic effects of NMN.
In plain wordsIn cells exposed to hypoxia, sirtinol blocked the antifibrotic effects of NMN.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseAntifibrotic effect blocked by sirtinol
Study
n: not reported in source
hypoxia-induced SVF cells
Outcome group
Organ injury · Metabolic and weight
Source sentences
Summary
In hypoxia-induced SVFs, the SIRT1 inhibitor sirtinol blocked the anti-fibrotic and anti-inflammatory effects of NMN, upregulated the HIF-1α and its acetylation level.
In this study, NMN (nicotinamide mononucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NMN (nicotinamide mononucleotide).
Show in the study text Report a problemFND-3677736105
06LabNot a test of NMN (nicotinamide mononucleotide) aloneIn vitro (cells)Mechanism
In hypoxic SVF cells, sirtinol blocked the anti-inflammatory effects of NMN.
In plain wordsIn cells exposed to hypoxia, sirtinol blocked the anti-inflammatory effects of NMN.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseAnti-inflammatory effect blocked by sirtinol
Study
n: not reported in source
hypoxia-induced SVF cells
Outcome group
Inflammation markers · Metabolic and weight
Source sentences
Summary
In hypoxia-induced SVFs, the SIRT1 inhibitor sirtinol blocked the anti-fibrotic and anti-inflammatory effects of NMN, upregulated the HIF-1α and its acetylation level.
In this study, NMN (nicotinamide mononucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NMN (nicotinamide mononucleotide).
Show in the study text Report a problemFND-3677736106
07LabNot a test of NMN (nicotinamide mononucleotide) aloneIn vitro (cells)Mechanism
In hypoxic SVF cells treated with NMN, sirtinol increased HIF-1α.
In plain wordsIn cells exposed to hypoxia and treated with NMN, sirtinol increased HIF-1α.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseHIF-1α with sirtinol
Study
n: not reported in source
hypoxia-induced SVF cells
Outcome group
Receptor activity and mechanism · Metabolic and weight
Source sentences
Summary
In hypoxia-induced SVFs, the SIRT1 inhibitor sirtinol blocked the anti-fibrotic and anti-inflammatory effects of NMN, upregulated the HIF-1α and its acetylation level.
In this study, NMN (nicotinamide mononucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NMN (nicotinamide mononucleotide).
Show in the study text Report a problemFND-3677736107
08LabNot a test of NMN (nicotinamide mononucleotide) aloneIn vitro (cells)Mechanism
In hypoxic SVF cells treated with NMN, sirtinol increased HIF-1α acetylation.
In plain wordsIn cells exposed to hypoxia and treated with NMN, sirtinol increased HIF-1α acetylation.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseHIF-1α acetylation with sirtinol
Study
n: not reported in source
hypoxia-induced SVF cells
Outcome group
Receptor activity and mechanism · Metabolic and weight
Source sentences
Summary
In hypoxia-induced SVFs, the SIRT1 inhibitor sirtinol blocked the anti-fibrotic and anti-inflammatory effects of NMN, upregulated the HIF-1α and its acetylation level.
In this study, NMN (nicotinamide mononucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NMN (nicotinamide mononucleotide).
Show in the study text Report a problemFND-3677736108
09LabNot a test of NMN (nicotinamide mononucleotide) aloneIn vitro (cells)Mechanism
In hypoxic SVF experiments testing NMN, the HIF1α stabilizer showed effects similar to sirtinol.
In plain wordsIn cells exposed to hypoxia, the HIF1α stabilizer showed effects similar to sirtinol in experiments testing NMN.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
Direction not reportedCoCl2 effects relative to sirtinol
Study
n: not reported in source
hypoxia-induced SVF cells
Outcome group
Receptor activity and mechanism · Metabolic and weight
Source sentences
Summary
The HIF1α stabilizer CoCl₂ showed similar effects as sirtinol.
1 context sentence(design, population, supporting numbers)
Summary · context
In hypoxia-induced SVFs, the SIRT1 inhibitor sirtinol blocked the anti-fibrotic and anti-inflammatory effects of NMN, upregulated the HIF-1α and its acetylation level.
In this study, NMN (nicotinamide mononucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NMN (nicotinamide mononucleotide).
Show in the study text Report a problemFND-3677736109

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

Subjects

Terms as the source lists them.

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