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Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin‐resistant men
Author(s) -
Dollerup Ole L.,
Chubanava Sabina,
Agerholm Marianne,
Søndergård Stine D.,
Altıntaş Ali,
Møller Andreas B.,
Høyer Kasper F.,
Ringgaard Steffen,
StødkildeJørgensen Hans,
Lavery Gareth G.,
Barrès Romain,
Larsen Steen,
Prats Clara,
Jessen Niels,
Treebak Jonas T.
Publication year - 2019
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp278752
Subject(s) - nicotinamide phosphoribosyltransferase , skeletal muscle , nad+ kinase , endocrinology , medicine , mitochondrion , biology , ucp3 , nicotinamide adenine dinucleotide , nicotinamide mononucleotide , sirtuin , oxidative phosphorylation , respiratory chain , sirtuin 1 , biochemistry , uncoupling protein , adipose tissue , brown adipose tissue , enzyme , downregulation and upregulation , gene
Key points This is the first long‐term human clinical trial to report on effects of nicotinamide riboside (NR) on skeletal muscle mitochondrial function, content and morphology. NR supplementation decreases nicotinamide phosphoribosyltransferase (NAMPT) protein abundance in skeletal muscle. NR supplementation does 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 oxidative phosphorylation Complex I, sirtuin 3 and succinate dehydrogenase.Abstract Preclinical evidence suggests 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 1000 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 quantitative PCR 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 by 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 sexes and potentially provide comparisons between young and older people.