Philp, A. M. | Search bioRxiv

bioRxiv2020

Nicotinamide Riboside supplementation does not alter whole-body or skeletal muscle metabolic responses to a single bout of endurance exercise

Oral supplementation of the NAD+ precursor Nicotinamide Riboside (NR) has been reported to increase Sirtuin (SIRT) signalling, mitochondrial biogenesis and endurance capacity in rodent skeletal muscle. However, whether NR supplementation can elicit a similar response in human skeletal muscle is unclear. This study aimed to assess the effect of 7-day NR supplementation on exercise-induced transduction and transcriptional responses in skeletal muscle of young, healthy, recreationally active human volunteers. In a double-blinded, randomised, counter-balanced, crossover design, eight male participants (age: 23 ± 4 years, VO2peak: 46.5 ± 4.4 mL·kg-1·min-1) received one week of NR or cellulose placebo (PLA) supplementation (1000 mg·d-1) before performing one hour of cycling at 60% Wmax. Muscle biopsies were collected prior to supplementation and pre-, immediately and three-hours post-exercise from the medial vastus lateralis, whilst venous blood samples were collected throughout the trial. Global acetylation, auto-PARylation of PARP1, acetylation of p53Lys382 and MnSODLys122 were unaffected by NR supplementation or exercise. Exercise led to an increase in AMPKThr172 (1.6-fold), and ACCSer79 (4-fold) phosphorylation, in addition to an increase in PGC-1α (∼5-fold) and PDK4 (∼10-fold) mRNA expression, however NR had no additional effect on this response. There was also no effect of NR supplementation on substrate utilisation at rest or during exercise or on skeletal muscle mitochondrial respiration. Finally, NR supplementation blunted the exercise induced activation of skeletal muscle NNMT mRNA expression, but had no effect on mRNA expression of NMRK1, NAMPT or NMNAT1, which were not significantly affected by NR supplementation or exercise. In summary, one week of NR supplementation does not augment skeletal muscle signal transduction pathways implicated in mitochondrial adaptation to endurance exercise.Competing Interest StatementThe authors have declared no competing interest.View Full Text

physiology↗

bioRxiv2020

Diet-Induced Vitamin D Deficiency Results in Reduced Skeletal Muscle Mitochondrial Respiration in C57BL/6J Mice

Vitamin D deficiency is known to be associated with symptoms of skeletal muscle myopathy including muscle weakness and fatigue. Recently, vitamin D related metabolites have been linked to the maintenance of mitochondrial function within skeletal muscle. However, current evidence is limited to in vitro models and the effects of diet-induced vitamin D deficiency upon skeletal muscle mitochondrial function in vivo have received little attention. In order to examine the role of vitamin D in the maintenance of mitochondrial function in vivo, we utilised an established model of diet-induced vitamin D deficiency in C57BL/6J mice. Mice were fed either a control (2,200 IU/kg) or a vitamin D deplete (0 IU/kg) diet for periods of 1-, 2- and 3-months. Skeletal muscle mitochondrial function and ADP sensitivity were assessed via high-resolution respirometry and mitochondrial protein content via immunoblotting. As a result of 3-month of diet-induced vitamin D deficiency, respiration supported via CI+IIP and ETC were 35% and 37% lower when compared to vitamin D replete mice (P < 0.05). Despite functional alterations, the protein expression of electron transfer chain subunits remained unchanged in response to dietary intervention (P > 0.05). In conclusion, we report that 3-months of diet-induced vitamin D deficiency reduced skeletal muscle mitochondrial function in C57BL/6J mice. Our data, when combined with previous in vitro observations, suggests that vitamin D mediated regulation of mitochondrial function may underlie the exacerbated muscle fatigue and performance deficits observed during vitamin D deficiency.

physiology↗