Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men.
Ole L DollerupSabina ChubanavaMarianne AgerholmStine D SøndergårdAli AltıntaşAndreas B MøllerKasper F HøyerSteffen RinggaardHans Stødkilde-JørgensenGareth G LaveryRomain BarrèsSteen LarsenClara PratsNiels JessenJonas T TreebakPublished in: The Journal of physiology (2019)
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.
Keyphrases
- skeletal muscle
- oxidative stress
- middle aged
- insulin resistance
- type diabetes
- high resolution
- gene expression
- clinical trial
- metabolic syndrome
- adipose tissue
- double blind
- weight loss
- placebo controlled
- squamous cell carcinoma
- stem cells
- protein protein
- bariatric surgery
- cell death
- south africa
- dna methylation
- electronic health record
- mesenchymal stem cells
- mass spectrometry
- deep learning
- current status
- phase ii
- reactive oxygen species
- microbial community
- data analysis
- network analysis