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Lapatto, H. A. K., Kuusela, M., Heikkinen, A., Muniandy, M., Van Der Kolk, B. W., Gopalakrishnan, S., Pöllänen, N., Sandvik, M., Schmidt, M. S., Heinonen, S., Saari, S., Kuula, J., Hakkarainen, A., Tampio, J., Saarinen, T., Taskinen, M.-R., Lundbom, N., Groop, P.-H., Tiirola, M., … Pirinen, E. (2023). Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. Science Advances, 9(2), eadd5163. https://doi.org/10.1126/sciadv.add5163

Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study

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Author: Lapatto, Helena A. K.1; Kuusela, Minna2; Heikkinen, Aino3;
Organizations: 1Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
2Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland
3Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
4Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland
5Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
6Department of Radiology, Medical Imaging Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
7Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland
8Population Health Unit, Finnish Institute for Health and Welfare, Oulu, Finland
9School of Pharmacy, University of Eastern Finland, Kuopio, Finland
10Abdominal Center, Department of Gastrointestinal Surgery, Helsinki University Hospital, Helsinki, Finland
11Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
12Abdominal Center, Nephrology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
13Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia
14Department of Environmental and Biological Sciences, University of Jyväskylä, FI-40014 Jyväskylä, Finland
15Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
16Department of Diabetes and Cancer Metabolism, City of Hope National Medical Center, Duarte, CA 91010, USA
17Faculty of Sport and Health Sciences, University of Jyväskylä, FI-40014 Jyväskylä, Finland
18Minerva Foundation Institute for Medical Research, Helsinki, Finland
19Abdominal Center, Healthy Weight Hub, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
20Research Unit of Biomedicine and Internal Medicine, Faculty of Medicine, University of Oulu, FIN-90220 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5.4 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2023071390607
Language: English
Published: American Association for the Advancement of Science, 2023
Publish Date: 2023-07-13
Description:

Abstract

Nicotinamide adenine dinucleotide (NAD⁺) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twenty body mass index (BMI)–discordant monozygotic twin pairs were supplemented with an escalating dose of NR (250 to 1000 mg/day) for 5 months. NR improved systemic NAD⁺ metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota composition in both cotwins. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue in both cotwins. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD⁺ metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.

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Series: Science advances
ISSN: 2375-2548
ISSN-E: 2375-2548
ISSN-L: 2375-2548
Volume: 9
Issue: 2
Article number: eadd5163
DOI: 10.1126/sciadv.add5163
OADOI: https://oadoi.org/10.1126/sciadv.add5163
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Subjects:
Article
Funding: This work was supported by Centre of Excellence funding from the Academy of Finland (#272376 to K.H.P. and #336823 to J.Ka.), Academy of Finland grants (286359, 314455, 335445, and Profi6 336449 to E.P.; 335443, 314383, 272376, and 266286 to K.H.P.; 308042 to S.P.; 297908 and 328685 to M.O.), Sigrid Jusélius Foundation (to K.H.P.), Finnish Medical Foundation (to H.A.K.L. and N.P.), Medical Society of Finland (to H.A.K.L.), Biomedicum Helsinki Foundation (to N.P.), Finnish Diabetes Research Foundation (to E.P.), Novo Nordisk Foundation (NNF20OC0060547, NNF17OC0027232, and NNF10OC1013354 to K.H.P.), Gyllenberg Foundation (to K.H.P.), Government Research Funds to Helsinki University Hospital (to K.H.P.), National Institutes of Health (R01HL147545 to C.B.), and Alfred E. Mann Family Foundation (to C.B.).
Copyright information: © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
  https://creativecommons.org/licenses/by/4.0/