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25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression

Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia), but the precise role of specific vitamin D metabolites in determining muscle phenot...

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Autores principales: Hassan-Smith, Zaki K., Jenkinson, Carl, Smith, David J., Hernandez, Ivan, Morgan, Stuart A., Crabtree, Nicola J., Gittoes, Neil J., Keevil, Brian G., Stewart, Paul M., Hewison, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310904/
https://www.ncbi.nlm.nih.gov/pubmed/28199350
http://dx.doi.org/10.1371/journal.pone.0170665
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author Hassan-Smith, Zaki K.
Jenkinson, Carl
Smith, David J.
Hernandez, Ivan
Morgan, Stuart A.
Crabtree, Nicola J.
Gittoes, Neil J.
Keevil, Brian G.
Stewart, Paul M.
Hewison, Martin
author_facet Hassan-Smith, Zaki K.
Jenkinson, Carl
Smith, David J.
Hernandez, Ivan
Morgan, Stuart A.
Crabtree, Nicola J.
Gittoes, Neil J.
Keevil, Brian G.
Stewart, Paul M.
Hewison, Martin
author_sort Hassan-Smith, Zaki K.
collection PubMed
description Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia), but the precise role of specific vitamin D metabolites in determining muscle phenotype and function is still unclear. To address this we quantified serum concentrations of multiple vitamin D metabolites, and assessed the impact of these metabolites on body composition/muscle function parameters, and muscle biopsy gene expression in a retrospective study of a cohort of healthy volunteers. Active serum 1,25-dihydroxyvitamin D3 (1α,25(OH)(2)D3), but not inactive 25-hydroxyvitamin D3 (25OHD3), correlated positively with measures of lower limb strength including power (rho = 0.42, p = 0.02), velocity (Vmax, rho = 0.40, p = 0.02) and jump height (rho = 0.36, p = 0.04). Lean mass correlated positively with 1α,25(OH)(2)D3 (rho = 0.47, p = 0.02), in women. Serum 25OHD3 and inactive 24,25-dihydroxyvitamin D3 (24,25(OH)(2)D3) had an inverse relationship with body fat (rho = -0.30, p = 0.02 and rho = -0.33, p = 0.01, respectively). Serum 25OHD3 and 24,25(OH)(2)D3 were also correlated with urinary steroid metabolites, suggesting a link with glucocorticoid metabolism. PCR array analysis of 92 muscle genes identified vitamin D receptor (VDR) mRNA in all muscle biopsies, with this expression being negatively correlated with serum 25OHD3, and Vmax, and positively correlated with fat mass. Of the other 91 muscle genes analysed by PCR array, 24 were positively correlated with 25OHD3, but only 4 were correlated with active 1α,25(OH)(2)D3. These data show that although 25OHD3 has potent actions on muscle gene expression, the circulating concentrations of this metabolite are more closely linked to body fat mass, suggesting that 25OHD3 can influence muscle function via indirect effects on adipose tissue. By contrast, serum 1α,25(OH)(2)D3 has limited effects on muscle gene expression, but is associated with increased muscle strength and lean mass in women. These pleiotropic effects of the vitamin D ‘metabolome’ on muscle function indicate that future supplementation studies should not be restricted to conventional analysis of the major circulating form of vitamin D, 25OHD3.
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spelling pubmed-53109042017-03-03 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression Hassan-Smith, Zaki K. Jenkinson, Carl Smith, David J. Hernandez, Ivan Morgan, Stuart A. Crabtree, Nicola J. Gittoes, Neil J. Keevil, Brian G. Stewart, Paul M. Hewison, Martin PLoS One Research Article Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia), but the precise role of specific vitamin D metabolites in determining muscle phenotype and function is still unclear. To address this we quantified serum concentrations of multiple vitamin D metabolites, and assessed the impact of these metabolites on body composition/muscle function parameters, and muscle biopsy gene expression in a retrospective study of a cohort of healthy volunteers. Active serum 1,25-dihydroxyvitamin D3 (1α,25(OH)(2)D3), but not inactive 25-hydroxyvitamin D3 (25OHD3), correlated positively with measures of lower limb strength including power (rho = 0.42, p = 0.02), velocity (Vmax, rho = 0.40, p = 0.02) and jump height (rho = 0.36, p = 0.04). Lean mass correlated positively with 1α,25(OH)(2)D3 (rho = 0.47, p = 0.02), in women. Serum 25OHD3 and inactive 24,25-dihydroxyvitamin D3 (24,25(OH)(2)D3) had an inverse relationship with body fat (rho = -0.30, p = 0.02 and rho = -0.33, p = 0.01, respectively). Serum 25OHD3 and 24,25(OH)(2)D3 were also correlated with urinary steroid metabolites, suggesting a link with glucocorticoid metabolism. PCR array analysis of 92 muscle genes identified vitamin D receptor (VDR) mRNA in all muscle biopsies, with this expression being negatively correlated with serum 25OHD3, and Vmax, and positively correlated with fat mass. Of the other 91 muscle genes analysed by PCR array, 24 were positively correlated with 25OHD3, but only 4 were correlated with active 1α,25(OH)(2)D3. These data show that although 25OHD3 has potent actions on muscle gene expression, the circulating concentrations of this metabolite are more closely linked to body fat mass, suggesting that 25OHD3 can influence muscle function via indirect effects on adipose tissue. By contrast, serum 1α,25(OH)(2)D3 has limited effects on muscle gene expression, but is associated with increased muscle strength and lean mass in women. These pleiotropic effects of the vitamin D ‘metabolome’ on muscle function indicate that future supplementation studies should not be restricted to conventional analysis of the major circulating form of vitamin D, 25OHD3. Public Library of Science 2017-02-15 /pmc/articles/PMC5310904/ /pubmed/28199350 http://dx.doi.org/10.1371/journal.pone.0170665 Text en © 2017 Hassan-Smith et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hassan-Smith, Zaki K.
Jenkinson, Carl
Smith, David J.
Hernandez, Ivan
Morgan, Stuart A.
Crabtree, Nicola J.
Gittoes, Neil J.
Keevil, Brian G.
Stewart, Paul M.
Hewison, Martin
25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression
title 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression
title_full 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression
title_fullStr 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression
title_full_unstemmed 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression
title_short 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression
title_sort 25-hydroxyvitamin d3 and 1,25-dihydroxyvitamin d3 exert distinct effects on human skeletal muscle function and gene expression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310904/
https://www.ncbi.nlm.nih.gov/pubmed/28199350
http://dx.doi.org/10.1371/journal.pone.0170665
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