scholarly journals Vitamin D Deficiency Promotes Skeletal Muscle Hypersensitivity and Sensory Hyperinnervation

2011 ◽  
Vol 31 (39) ◽  
pp. 13728-13738 ◽  
Author(s):  
S. E. Tague ◽  
G. L. Clarke ◽  
M. K. Winter ◽  
K. E. McCarson ◽  
D. E. Wright ◽  
...  
2020 ◽  
Author(s):  
Emma L Watson ◽  
Thomas J Wilkinson ◽  
Tom F O’Sullivan ◽  
Luke A Baker ◽  
Douglas W Gould ◽  
...  

AbstractEvidence is growing for a role of vitamin D in regulating skeletal muscle mass, strength and functional capacity. Given the role the kidneys play in activating total vitamin D, and the high prevalence of vitamin D deficiency in Chronic Kidney Disease (CKD), it is possible that deficiency contributes to the low levels of physical function and muscle mass in these patients. This is a secondary cross-sectional analysis of previously published interventional study, with ex vivo follow up work. 34 CKD patients at stages G3b-5 (eGFR 25.5 ± 8.3ml/min/1.73m2; age 61 ± 12 years) were recruited, with a sub-group (n=20) also donating a muscle biopsy. Vitamin D and associated metabolites were analysed in plasma by liquid chromatography tandem-mass spectroscopy and correlated to a range of physiological tests of muscle size, function, exercise capacity and body composition. The effects of 1α,25(OH)2D3 supplementation on myogenesis and myotube size was investigated in primary skeletal muscle cells from vitamin D deficient donors. In vivo, there was no association between total or active vitamin D and muscle size or strength, but a significant correlation with was seen with the total form. Ex vivo, 1α,25(OH)2D3 supplementation reduced IL-6 mRNA expression, but had no effect upon proliferation, differentiation or myotube diameter. This early preliminary work suggests that vitamin D deficiency is not a prominent factor driving the loss of muscle mass in CKD, but may play a role in reduced exercise capacity.


2015 ◽  
Vol 31 (3) ◽  
pp. 585-595 ◽  
Author(s):  
Songcang Chen ◽  
S Armando Villalta ◽  
Devendra K Agrawal

2014 ◽  
Vol 11 (1) ◽  
pp. 47 ◽  
Author(s):  
Carla Domingues-Faria ◽  
Audrey Chanet ◽  
Jérôme Salles ◽  
Alexandre Berry ◽  
Christophe Giraudet ◽  
...  

1983 ◽  
Vol 72 (1) ◽  
pp. 102-112 ◽  
Author(s):  
S J Wassner ◽  
J B Li ◽  
A Sperduto ◽  
M E Norman

2021 ◽  
Vol 249 (2) ◽  
pp. 113-124
Author(s):  
Stephen P Ashcroft ◽  
Gareth Fletcher ◽  
Ashleigh M Philp ◽  
Carl Jenkinson ◽  
Shatarupa Das ◽  
...  

Vitamin D deficiency is 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 either fed a control diet (2200 IU/kg i.e. vitamin D replete) or a vitamin D-deplete (0 IU/kg) diet for periods of 1, 2 and 3 months. Gastrocnemius muscle mitochondrial function and ADP sensitivity were assessed via high-resolution respirometry and mitochondrial protein content via immunoblotting. As a result of 3 months of diet-induced vitamin D deficiency, respiration supported via complex I + II (CI + IIP) and the electron transport chain (ETC) were 35 and 37% lower when compared to vitamin D-replete mice (P < 0.05). Despite functional alterations, citrate synthase activity, AMPK phosphorylation, mitofilin, OPA1 and ETC subunit protein content 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 respiration in C57BL/6J mice. Our data, when combined with previous in vitro observations, suggest that vitamin D-mediated regulation of mitochondrial function may underlie the exacerbated muscle fatigue and performance deficits observed during vitamin D deficiency.


Endocrinology ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 347-357 ◽  
Author(s):  
Christian M. Girgis ◽  
Roderick J. Clifton-Bligh ◽  
Nancy Mokbel ◽  
Kim Cheng ◽  
Jenny E. Gunton

Vitamin D deficiency is linked to a range of muscle disorders including myalgia, muscle weakness, and falls. Humans with severe vitamin D deficiency and mice with transgenic vitamin D receptor (VDR) ablation have muscle fiber atrophy. However, molecular mechanisms by which vitamin D influences muscle function and fiber size remain unclear. A central question is whether VDR is expressed in skeletal muscle and is able to regulate transcription at this site. To address this, we examined key molecular and morphologic changes in C2C12 cells treated with 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)2D). As well as stimulating VDR expression, 25(OH)D and 1,25(OH)2D dose-dependently increased expression of the classic vitamin D target cytochrome P450, family 24, subfamily A, polypeptide 1 (CYP24A1), demonstrating the presence of an autoregulatory vitamin D-endocrine system in these cells. Luciferase reporter studies demonstrated that cytochrome P450, family 27, subfamily B, polypeptide 1 (CYP27B1) was functional in these cells. Both 25OHD and 1,25(OH)2D altered C2C12 proliferation and differentiation. These effects were related to the increased expression of genes involved in G0/G1 arrest (retinoblastoma protein [Rb], 1.3-fold; ATM, 1.5-fold, both P &lt; .05), downregulation of mRNAs involved in G1/S transition, including myc and cyclin-D1 (0.7- and 0.8-fold, both P &lt; .05) and reduced phosphorylation of Rb protein (0.3-fold, P &lt; .005). After serum depletion, 1,25(OH)2D (100nM) suppressed myotube formation with decreased mRNAs for key myogenic regulatory factors (myogenin, 0.5-fold; myf5, 0.4-fold, P &lt; .005) but led to a 1.8-fold increase in cross-sectional size of individual myotubes associated with markedly decreased myostatin expression (0.2-fold, P &lt; .005). These data show that vitamin D signaling alters gene expression in C2C12 cells, with effects on proliferation, differentiation, and myotube size.


2015 ◽  
Vol 44 (suppl 2) ◽  
pp. ii13.4-ii13 ◽  
Author(s):  
T. Ong ◽  
K. Tsintzas ◽  
L. Daunt ◽  
O. Sahota

2012 ◽  
Vol 34 (1) ◽  
pp. 33-83 ◽  
Author(s):  
Christian M. Girgis ◽  
Roderick J. Clifton-Bligh ◽  
Mark W. Hamrick ◽  
Michael F. Holick ◽  
Jenny E. Gunton

Abstract Beyond its established role in bone and mineral homeostasis, there is emerging evidence that vitamin D exerts a range of effects in skeletal muscle. Reports of profound muscle weakness and changes in the muscle morphology of adults with vitamin D deficiency have long been described. These reports have been supplemented by numerous trials assessing the impact of vitamin D on muscle strength and mass and falls in predominantly elderly and deficient populations. At a basic level, animal models have confirmed that vitamin D deficiency and congenital aberrations in the vitamin D endocrine system may result in muscle weakness. To explain these effects, some molecular mechanisms by which vitamin D impacts on muscle cell differentiation, intracellular calcium handling, and genomic activity have been elucidated. There are also suggestions that vitamin D alters muscle metabolism, specifically its sensitivity to insulin, which is a pertinent feature in the pathophysiology of insulin resistance and type 2 diabetes. We will review the range of human clinical, animal, and cell studies that address the impact of vitamin D in skeletal muscle, and discuss the controversial issues. This is a vibrant field of research and one that continues to extend the frontiers of knowledge of vitamin D's broad functional repertoire.


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