Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin resistant men

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Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin resistant men. / Dollerup, Ole L; Chubanava, Sabina; Agerholm, Marianne; Søndergård, Stine D; Altıntaş, Ali; Møller, Andreas B; Høyer, Kasper F; Ringgaard, Steffen; Stødkilde-Jørgensen, Hans; Lavery, Gareth G; Barrès, Romain; Larsen, Steen; Prats, Clara; Jessen, Niels; Treebak, Jonas T.

In: The Journal of Physiology, Vol. 598, No. 4, 02.2020, p. 731-754.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Dollerup, OL, Chubanava, S, Agerholm, M, Søndergård, SD, Altıntaş, A, Møller, AB, Høyer, KF, Ringgaard, S, Stødkilde-Jørgensen, H, Lavery, GG, Barrès, R, Larsen, S, Prats, C, Jessen, N & Treebak, JT 2020, 'Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin resistant men', The Journal of Physiology, vol. 598, no. 4, pp. 731-754. https://doi.org/10.1113/JP278752

APA

Dollerup, O. L., Chubanava, S., Agerholm, M., Søndergård, S. D., Altıntaş, A., Møller, A. B., Høyer, K. F., Ringgaard, S., Stødkilde-Jørgensen, H., Lavery, G. G., Barrès, R., Larsen, S., Prats, C., Jessen, N., & Treebak, J. T. (2020). Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin resistant men. The Journal of Physiology, 598(4), 731-754. https://doi.org/10.1113/JP278752

CBE

Dollerup OL, Chubanava S, Agerholm M, Søndergård SD, Altıntaş A, Møller AB, Høyer KF, Ringgaard S, Stødkilde-Jørgensen H, Lavery GG, Barrès R, Larsen S, Prats C, Jessen N, Treebak JT. 2020. Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin resistant men. The Journal of Physiology. 598(4):731-754. https://doi.org/10.1113/JP278752

MLA

Vancouver

Dollerup OL, Chubanava S, Agerholm M, Søndergård SD, Altıntaş A, Møller AB et al. Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin resistant men. The Journal of Physiology. 2020 Feb;598(4):731-754. https://doi.org/10.1113/JP278752

Author

Dollerup, Ole L ; Chubanava, Sabina ; Agerholm, Marianne ; Søndergård, Stine D ; Altıntaş, Ali ; Møller, Andreas B ; Høyer, Kasper F ; Ringgaard, Steffen ; Stødkilde-Jørgensen, Hans ; Lavery, Gareth G ; Barrès, Romain ; Larsen, Steen ; Prats, Clara ; Jessen, Niels ; Treebak, Jonas T. / Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin resistant men. In: The Journal of Physiology. 2020 ; Vol. 598, No. 4. pp. 731-754.

Bibtex

@article{99e2d0f315224e27b78ca84eb0e970d4,
title = "Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin resistant men",
abstract = "KEY POINTS: •This is the first long-term human clinical trial to report on effects of NR on skeletal muscle mitochondrial function, content and morphology •NR supplementation decreases NAMPT protein abundance in skeletal muscle •NR supplementation do not affect NAD metabolite concentrations in skeletal muscle •Respiration, distribution, and quantity of muscle mitochondria are unaffected by NR •NAMPT in skeletal muscle correlates positively with OXPHOS Complex I, SIRT3, and SDH ABSTRACT: Preclinical evidence suggest that the nicotinamide adenine dinucleotide (NAD+ ) precursor nicotinamide riboside (NR) boosts NAD+ levels and improves diseases associated with mitochondrial dysfunction. We aimed to determine if dietary NR supplementation in middle-aged, obese, insulin-resistant men affects mitochondrial respiration, content, and morphology in skeletal muscle. In a randomized, placebo-controlled clinical trial, 40 participants received 1,000 mg NR or placebo twice daily for 12 weeks. Skeletal muscle biopsies were collected before and after the intervention. Mitochondrial respiratory capacity was determined by high-resolution respirometry on single muscle fibres. Protein abundance and mRNA expression were measured by Western blot and qPCR analyses, respectively, and in a subset of the participants (placebo n = 8; NR n = 8) we quantified mitochondrial fractional area and mitochondrial morphology by laser scanning confocal microscopy. Protein levels of nicotinamide phosphoribosyltransferase (NAMPT), an essential NAD+ biosynthetic enzyme in skeletal muscle, decreased 14% with NR. However, steady-state NAD+ levels as well as gene expression and protein abundance of other NAD+ biosynthetic enzymes remained unchanged. Neither respiratory capacity of skeletal muscle mitochondria nor abundance of mitochondrial associated proteins were affected by NR. Moreover, no changes in mitochondrial fractional area or network morphology were observed. Our data do not support the hypothesis that dietary NR supplementation has significant impact on skeletal muscle mitochondria in obese and insulin-resistant men. Future studies on the effects of NR on human skeletal muscle may include both genders and potentially provide comparisons between young and older people. This article is protected by copyright. All rights reserved.",
keywords = "NAD, NAMPT, human skeletal muscle, mitochondria, nicotinamide riboside",
author = "Dollerup, {Ole L} and Sabina Chubanava and Marianne Agerholm and S{\o}nderg{\aa}rd, {Stine D} and Ali Altınta{\c s} and M{\o}ller, {Andreas B} and H{\o}yer, {Kasper F} and Steffen Ringgaard and Hans St{\o}dkilde-J{\o}rgensen and Lavery, {Gareth G} and Romain Barr{\`e}s and Steen Larsen and Clara Prats and Niels Jessen and Treebak, {Jonas T}",
note = "This article is protected by copyright. All rights reserved.",
year = "2020",
month = feb,
doi = "10.1113/JP278752",
language = "English",
volume = "598",
pages = "731--754",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell Publishing Ltd.",
number = "4",

}

RIS

TY - JOUR

T1 - Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin resistant men

AU - Dollerup, Ole L

AU - Chubanava, Sabina

AU - Agerholm, Marianne

AU - Søndergård, Stine D

AU - Altıntaş, Ali

AU - Møller, Andreas B

AU - Høyer, Kasper F

AU - Ringgaard, Steffen

AU - Stødkilde-Jørgensen, Hans

AU - Lavery, Gareth G

AU - Barrès, Romain

AU - Larsen, Steen

AU - Prats, Clara

AU - Jessen, Niels

AU - Treebak, Jonas T

N1 - This article is protected by copyright. All rights reserved.

PY - 2020/2

Y1 - 2020/2

N2 - KEY POINTS: •This is the first long-term human clinical trial to report on effects of NR on skeletal muscle mitochondrial function, content and morphology •NR supplementation decreases NAMPT protein abundance in skeletal muscle •NR supplementation do not affect NAD metabolite concentrations in skeletal muscle •Respiration, distribution, and quantity of muscle mitochondria are unaffected by NR •NAMPT in skeletal muscle correlates positively with OXPHOS Complex I, SIRT3, and SDH ABSTRACT: Preclinical evidence suggest that the nicotinamide adenine dinucleotide (NAD+ ) precursor nicotinamide riboside (NR) boosts NAD+ levels and improves diseases associated with mitochondrial dysfunction. We aimed to determine if dietary NR supplementation in middle-aged, obese, insulin-resistant men affects mitochondrial respiration, content, and morphology in skeletal muscle. In a randomized, placebo-controlled clinical trial, 40 participants received 1,000 mg NR or placebo twice daily for 12 weeks. Skeletal muscle biopsies were collected before and after the intervention. Mitochondrial respiratory capacity was determined by high-resolution respirometry on single muscle fibres. Protein abundance and mRNA expression were measured by Western blot and qPCR analyses, respectively, and in a subset of the participants (placebo n = 8; NR n = 8) we quantified mitochondrial fractional area and mitochondrial morphology by laser scanning confocal microscopy. Protein levels of nicotinamide phosphoribosyltransferase (NAMPT), an essential NAD+ biosynthetic enzyme in skeletal muscle, decreased 14% with NR. However, steady-state NAD+ levels as well as gene expression and protein abundance of other NAD+ biosynthetic enzymes remained unchanged. Neither respiratory capacity of skeletal muscle mitochondria nor abundance of mitochondrial associated proteins were affected by NR. Moreover, no changes in mitochondrial fractional area or network morphology were observed. Our data do not support the hypothesis that dietary NR supplementation has significant impact on skeletal muscle mitochondria in obese and insulin-resistant men. Future studies on the effects of NR on human skeletal muscle may include both genders and potentially provide comparisons between young and older people. This article is protected by copyright. All rights reserved.

AB - KEY POINTS: •This is the first long-term human clinical trial to report on effects of NR on skeletal muscle mitochondrial function, content and morphology •NR supplementation decreases NAMPT protein abundance in skeletal muscle •NR supplementation do not affect NAD metabolite concentrations in skeletal muscle •Respiration, distribution, and quantity of muscle mitochondria are unaffected by NR •NAMPT in skeletal muscle correlates positively with OXPHOS Complex I, SIRT3, and SDH ABSTRACT: Preclinical evidence suggest that the nicotinamide adenine dinucleotide (NAD+ ) precursor nicotinamide riboside (NR) boosts NAD+ levels and improves diseases associated with mitochondrial dysfunction. We aimed to determine if dietary NR supplementation in middle-aged, obese, insulin-resistant men affects mitochondrial respiration, content, and morphology in skeletal muscle. In a randomized, placebo-controlled clinical trial, 40 participants received 1,000 mg NR or placebo twice daily for 12 weeks. Skeletal muscle biopsies were collected before and after the intervention. Mitochondrial respiratory capacity was determined by high-resolution respirometry on single muscle fibres. Protein abundance and mRNA expression were measured by Western blot and qPCR analyses, respectively, and in a subset of the participants (placebo n = 8; NR n = 8) we quantified mitochondrial fractional area and mitochondrial morphology by laser scanning confocal microscopy. Protein levels of nicotinamide phosphoribosyltransferase (NAMPT), an essential NAD+ biosynthetic enzyme in skeletal muscle, decreased 14% with NR. However, steady-state NAD+ levels as well as gene expression and protein abundance of other NAD+ biosynthetic enzymes remained unchanged. Neither respiratory capacity of skeletal muscle mitochondria nor abundance of mitochondrial associated proteins were affected by NR. Moreover, no changes in mitochondrial fractional area or network morphology were observed. Our data do not support the hypothesis that dietary NR supplementation has significant impact on skeletal muscle mitochondria in obese and insulin-resistant men. Future studies on the effects of NR on human skeletal muscle may include both genders and potentially provide comparisons between young and older people. This article is protected by copyright. All rights reserved.

KW - NAD

KW - NAMPT

KW - human skeletal muscle

KW - mitochondria

KW - nicotinamide riboside

U2 - 10.1113/JP278752

DO - 10.1113/JP278752

M3 - Journal article

C2 - 31710095

VL - 598

SP - 731

EP - 754

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 4

ER -