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Domingues-Faria C, Chanet A, Salles J, et al. Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old wistar rats. Nutr Metab (Lond). 2014;11(1):47doi: 10.1186/1743-7075-11-47.
Domingues-Faria, C., Chanet, A., Salles, J., Berry, A., Giraudet, C., Patrac, V., Denis, P., Bouton, K., Goncalves-Mendes, N., Vasson, M. P., Boirie, Y., & Walrand, S. (2014). Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old wistar rats. Nutrition & metabolism, 11(1), 47. https://doi.org/10.1186/1743-7075-11-47
Domingues-Faria, Carla, et al. "Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old wistar rats." Nutrition & metabolism vol. 11,1 (2014): 47. doi: https://doi.org/10.1186/1743-7075-11-47
Domingues-Faria C, Chanet A, Salles J, Berry A, Giraudet C, Patrac V, Denis P, Bouton K, Goncalves-Mendes N, Vasson MP, Boirie Y, Walrand S. Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old wistar rats. Nutr Metab (Lond). 2014 Sep 30;11(1):47. doi: 10.1186/1743-7075-11-47. eCollection 2014. PMID: 25317198; PMCID: PMC4195890.
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Nutr Metab (Lond). 2014 Sep 30;11(1):47. doi: 10.1186/1743-7075-11-47. eCollection 2014.

Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old wistar rats.

Nutrition & metabolism

Carla Domingues-Faria, Audrey Chanet, Jérôme Salles, Alexandre Berry, Christophe Giraudet, Véronique Patrac, Philippe Denis, Katia Bouton, Nicolas Goncalves-Mendes, Marie-Paule Vasson, Yves Boirie, Stéphane Walrand

Affiliations

  1. Université d'Auvergne, Unité de Nutrition Humaine, Equipe ECREIN, CLARA, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
  2. Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
  3. Université d'Auvergne, Unité de Nutrition Humaine, Installation Expérimentale de Nutrition, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
  4. Université d'Auvergne, Unité de Nutrition Humaine, Equipe ECREIN, CLARA, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France.
  5. Université d'Auvergne, Unité de Nutrition Humaine, Equipe ECREIN, CLARA, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; Centre Jean Perrin, Unité de Nutrition, 63000 Clermont-Ferrand, France.
  6. Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; CHU Clermont-Ferrand, Service de Nutrition Clinique, 63003 Clermont-Ferrand, France.

PMID: 25317198 PMCID: PMC4195890 DOI: 10.1186/1743-7075-11-47

Abstract

BACKGROUND: The diminished ability of aged muscle to self-repair is a factor behind sarcopenia and contributes to muscle atrophy. Muscle repair depends on satellite cells whose pool size is diminished with aging. A reduction in Notch pathway activity may explain the age-related decrease in satellite cell proliferation, as this pathway has been implicated in satellite cell self-renewal. Skeletal muscle is a target of vitamin D which modulates muscle cell proliferation and differentiation in vitro and stimulates muscle regeneration in vivo. Vitamin D status is positively correlated to muscle strength/function, and elderly populations develop a vitamin D deficiency. The aim of this study was to evaluate how vitamin D deficiency induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential in muscle.

METHODS: 15-month-old male rats were vitamin D-depleted or not (control) for 9 months (n = 10 per group). Rats were 24-month-old at the end of the experiment. Gene and/or protein expression of markers of proliferation, or modulating proliferation, and of Notch signalling pathway were studied in the tibialis anterior muscle by qPCR and western blot. An unpaired student's t-test was performed to test the effect of the experimental conditions.

RESULTS: Vitamin D depletion led to a drop in concentrations of plasma 25-hydroxyvitamin D in depleted rats compared to controls (-74%, p < 0.01). Tibialis anterior weight was decreased in D-depleted rats (-25%, p < 0.05). The D-depleted group showed -39%, -31% drops in expression of two markers known to modulate proliferation (Bmp4, Fgf-2 mRNA levels) and -56% drop in one marker of cell proliferation (PCNA protein expression) compared to controls (p < 0.05). Notch pathway activity was blunted in tibialis anterior of D-depleted rats compared to controls, seen as a down-regulation of cleaved Notch (-53%, p < 0.05) and its target Hes1 (-35%, p < 0.05).

CONCLUSIONS: A 9-month vitamin D depletion induced vitamin D deficiency in old rats. Vitamin D depletion induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential. Vitamin D deficiency could aggravate the age-related decrease in muscle regeneration capacity.

Keywords: Aging; Notch signalling; Skeletal muscle atrophy; Vitamin D deficiency

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