NAD replenishment restores mitochondrial function and thermogenesis in the brown adipose tissue of mice with obesity.

Braga RR, Rocha MB, Morelli AP, da Costa RG, Mori MAS, da Silva ASR, Pauli JR, Cintra DE, Ropelle ER

The Journal of physiology5 May 2025Cited by 4 (Europe PMC)

PMID40320990DOI10.1113/jp288453PepBankPUB-40320990

Publisher page PubMedAsk about this study

Summary

Brown adipose tissue (BAT) is a highly specialized thermogenic tissue and plays a critical role in controlling energy expenditure and metabolic homeostasis. BAT dysfunction is associated with body weight gain and metabolic disorders in mice models. Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function. Using a wide multi-omics and phenotypic panel of isogenic strains of BXD mice, we found that the NAD-biosynthesis pathway in BAT is closely associated with body weight gain, adiposity, insulin resistance, oxygen consumption, exercise capacity and mitochondrial metabolism. Interestingly, the high-fat diet (HFD) treatment disrupted the NAD-biosynthesis pathway, reducing Nampt and NMNat3 protein contents and inducing severe mitochondrial dysfunction in BAT of mice. Finally, the oral treatment with nicotinamide riboside (NR), an NAD⁺ precursor, significantly boosted NAD⁺ levels and preserved the morphofunctional mitochondria aspects of mitochondria, and the thermogenesis capacity of BAT in HFD-fed mice. These data point to the NAD synthesis pathway as a promising therapeutic adjuvant target in body thermogenesis management. KEY POINTS: Obesity impairs the NAD⁺ biosynthesis pathway, leading to mitochondrial dysfunction and reduced thermogenic capacity. NAD⁺ metabolism enzymes Nampt and NMNat3 are crucial for mitochondrial function in BAT. Nicotinamide riboside treatment increases the expression of key thermogenic proteins and NAD⁺-related enzymes in BAT, optimizing adaptive thermogenesis and mitochondria function.

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

Results from this study15

No result from this study comes from a test of the peptide.

Natural levels measured1

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01AnimalEndogenous levelAnimal study (in vivo)Mechanism
In HFD-fed mice, oral nicotinamide riboside increased natural NAD levels in brown adipose tissue.
In plain wordsIn mice fed a high-fat diet, nicotinamide riboside increased the body's own NAD levels.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreaseNAD levels after NR
Study
mousen: not reported in source
HFD-fed mice
Outcome group
Mitochondrial function · Metabolic and weight
Source sentences
Summary
Finally, the oral treatment with nicotinamide riboside (NR), an NAD⁺ precursor, significantly boosted NAD⁺ levels and preserved the morphofunctional mitochondria aspects of mitochondria, and the thermogenesis capacity of BAT in HFD-fed mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
This result measures the body's own NAD+ (nicotinamide adenine dinucleotide). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4032099010

Studies that did not test the peptide alone14

In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).

02AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Other
In BXD mice, the NAD-biosynthesis pathway in brown adipose tissue was associated with body weight gain.
In plain wordsIn mice, the NAD-biosynthesis pathway was linked to body weight gain.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Direction not reportedBody weight gain association
Study
mousen: not reported in source
BXD mice
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
Using a wide multi-omics and phenotypic panel of isogenic strains of BXD mice, we found that the NAD-biosynthesis pathway in BAT is closely associated with body weight gain, adiposity, insulin resistance, oxygen consumption, exercise capacity and mitochondrial metabolism.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099001
03AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Other
In BXD mice, the NAD-biosynthesis pathway in brown adipose tissue was associated with adiposity.
In plain wordsIn mice, the NAD-biosynthesis pathway was linked to body fat.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Direction not reportedAdiposity association
Study
mousen: not reported in source
BXD mice
Outcome group
Body composition · Metabolic and weight
Source sentences
Summary
Using a wide multi-omics and phenotypic panel of isogenic strains of BXD mice, we found that the NAD-biosynthesis pathway in BAT is closely associated with body weight gain, adiposity, insulin resistance, oxygen consumption, exercise capacity and mitochondrial metabolism.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099002
04AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Other
In BXD mice, the NAD-biosynthesis pathway was associated with insulin resistance.
In plain wordsIn mice, the NAD-biosynthesis pathway was linked to insulin resistance.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Direction not reportedInsulin resistance association
Study
mousen: not reported in source
BXD mice
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Using a wide multi-omics and phenotypic panel of isogenic strains of BXD mice, we found that the NAD-biosynthesis pathway in BAT is closely associated with body weight gain, adiposity, insulin resistance, oxygen consumption, exercise capacity and mitochondrial metabolism.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099003
05AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Other
In BXD mice, the NAD-biosynthesis pathway was associated with oxygen consumption.
In plain wordsIn mice, the NAD-biosynthesis pathway was linked to oxygen consumption.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Direction not reportedOxygen consumption association
Study
mousen: not reported in source
BXD mice
Outcome group
Mitochondrial function · Metabolic and weight
Source sentences
Summary
Using a wide multi-omics and phenotypic panel of isogenic strains of BXD mice, we found that the NAD-biosynthesis pathway in BAT is closely associated with body weight gain, adiposity, insulin resistance, oxygen consumption, exercise capacity and mitochondrial metabolism.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099004
06AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Other
In BXD mice, the NAD-biosynthesis pathway was associated with exercise capacity.
In plain wordsIn mice, the NAD-biosynthesis pathway was linked to exercise capacity.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Direction not reportedExercise capacity association
Study
mousen: not reported in source
BXD mice
Outcome group
Exercise and physical function · Musculoskeletal
Source sentences
Summary
Using a wide multi-omics and phenotypic panel of isogenic strains of BXD mice, we found that the NAD-biosynthesis pathway in BAT is closely associated with body weight gain, adiposity, insulin resistance, oxygen consumption, exercise capacity and mitochondrial metabolism.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099005
07AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Other
In BXD mice, the NAD-biosynthesis pathway was associated with mitochondrial metabolism.
In plain wordsIn mice, the NAD-biosynthesis pathway was linked to mitochondrial metabolism.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Direction not reportedMitochondrial metabolism association
Study
mousen: not reported in source
BXD mice
Outcome group
Mitochondrial function · Metabolic and weight
Source sentences
Summary
Using a wide multi-omics and phenotypic panel of isogenic strains of BXD mice, we found that the NAD-biosynthesis pathway in BAT is closely associated with body weight gain, adiposity, insulin resistance, oxygen consumption, exercise capacity and mitochondrial metabolism.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099006
08AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Mechanism
In mice, a high-fat diet disrupted NAD biosynthesis and reduced Nampt protein content in brown adipose tissue.
In plain wordsIn mice, a high-fat diet reduced Nampt protein in the NAD-biosynthesis pathway.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
DecreaseNampt protein content
Study
mousen: not reported in source
BXD mice
Outcome group
Receptor activity and mechanism · Metabolic and weight
Source sentences
Summary
Interestingly, the high-fat diet (HFD) treatment disrupted the NAD-biosynthesis pathway, reducing Nampt and NMNat3 protein contents and inducing severe mitochondrial dysfunction in BAT of mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099007
09AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Mechanism
In mice, a high-fat diet disrupted NAD biosynthesis and reduced NMNat3 protein content in brown adipose tissue.
In plain wordsIn mice, a high-fat diet reduced NMNat3 protein in the NAD-biosynthesis pathway.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
DecreaseNMNat3 protein content
Study
mousen: not reported in source
BXD mice
Outcome group
Receptor activity and mechanism · Metabolic and weight
Source sentences
Summary
Interestingly, the high-fat diet (HFD) treatment disrupted the NAD-biosynthesis pathway, reducing Nampt and NMNat3 protein contents and inducing severe mitochondrial dysfunction in BAT of mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099008
10AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Mechanism
In mice, a high-fat diet disrupted NAD biosynthesis and induced mitochondrial dysfunction in brown adipose tissue.
In plain wordsIn mice, a high-fat diet disrupted NAD biosynthesis and damaged mitochondrial function.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreaseMitochondrial dysfunction
Study
mousen: not reported in source
BXD mice
Outcome group
Mitochondrial function · Metabolic and weight
Source sentences
Summary
Interestingly, the high-fat diet (HFD) treatment disrupted the NAD-biosynthesis pathway, reducing Nampt and NMNat3 protein contents and inducing severe mitochondrial dysfunction in BAT of mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099009
11AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Efficacy outcome
In HFD-fed mice, nicotinamide riboside, an NAD precursor, preserved mitochondrial morphology in brown adipose tissue.
In plain wordsIn mice fed a high-fat diet, the NAD precursor nicotinamide riboside preserved mitochondrial structure.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Not applicableMitochondrial morphology
Study
mousen: not reported in source
HFD-fed mice
Outcome group
Mitochondrial function · Metabolic and weight
Source sentences
Summary
Finally, the oral treatment with nicotinamide riboside (NR), an NAD⁺ precursor, significantly boosted NAD⁺ levels and preserved the morphofunctional mitochondria aspects of mitochondria, and the thermogenesis capacity of BAT in HFD-fed mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099011
12AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Efficacy outcome
In HFD-fed mice, nicotinamide riboside, an NAD precursor, preserved mitochondrial function in brown adipose tissue.
In plain wordsIn mice fed a high-fat diet, the NAD precursor nicotinamide riboside preserved mitochondrial function.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Not applicableMitochondrial function
Study
mousen: not reported in source
HFD-fed mice
Outcome group
Mitochondrial function · Metabolic and weight
Source sentences
Summary
Finally, the oral treatment with nicotinamide riboside (NR), an NAD⁺ precursor, significantly boosted NAD⁺ levels and preserved the morphofunctional mitochondria aspects of mitochondria, and the thermogenesis capacity of BAT in HFD-fed mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099012
13AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Efficacy outcome
In HFD-fed mice, nicotinamide riboside, an NAD precursor, preserved brown adipose tissue thermogenesis capacity.
In plain wordsIn mice fed a high-fat diet, the NAD precursor nicotinamide riboside preserved heat production in brown fat.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Not applicableThermogenesis capacity
Study
mousen: not reported in source
HFD-fed mice
Outcome group
Energy expenditure and thermogenesis · Metabolic and weight
Source sentences
Summary
Finally, the oral treatment with nicotinamide riboside (NR), an NAD⁺ precursor, significantly boosted NAD⁺ levels and preserved the morphofunctional mitochondria aspects of mitochondria, and the thermogenesis capacity of BAT in HFD-fed mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099013
14AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Mechanism
In mice, the NAD precursor nicotinamide riboside increased expression of key thermogenic proteins in brown adipose tissue.
In plain wordsIn mice, the NAD precursor nicotinamide riboside increased key heat-producing proteins in brown fat.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreaseThermogenic protein expression
Study
mousen: not reported in source
BXD mice
Outcome group
Energy expenditure and thermogenesis · Metabolic and weight
Source sentences
Summary
Nicotinamide riboside treatment increases the expression of key thermogenic proteins and NAD⁺-related enzymes in BAT, optimizing adaptive thermogenesis and mitochondria function.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099014
15AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Mechanism
In mice, nicotinamide riboside increased expression of NAD-related enzymes in brown adipose tissue.
In plain wordsIn mice, nicotinamide riboside increased NAD-related enzymes in brown fat.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreaseNAD-related enzyme expression
Study
mousen: not reported in source
BXD mice
Outcome group
Receptor activity and mechanism · Metabolic and weight
Source sentences
Summary
Nicotinamide riboside treatment increases the expression of key thermogenic proteins and NAD⁺-related enzymes in BAT, optimizing adaptive thermogenesis and mitochondria function.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we investigated the influence of the NAD-biosynthesis pathway in the control of BAT metabolism and function.
In this study, NAD+ (nicotinamide adenine dinucleotide) 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 NAD+ (nicotinamide adenine dinucleotide).
Show in the study text Report a problemFND-4032099015

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
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

Journal Article

Keywords

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