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

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 - Nutr Metab (Lond) (2014)

Bottom Line: Muscle repair depends on satellite cells whose pool size is diminished with aging.An unpaired student's t-test was performed to test the effect of the experimental conditions.Vitamin D deficiency could aggravate the age-related decrease in muscle regeneration capacity.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of vitamin D depletion ontibialis anteriororsoleus/body weight ratio. On the day of euthanasia, tibialis anterior (TA) (A) and soleus(B) of control and depleted rats were removed and weighed. TA or soleus/body weight ratio was calculated for each rat (n = 7 for control group and n = 9 for depleted group). TA/body weight ratio decreased in vitamin D-depleted old rats compared to control rats, whereas soleus/body weight ratio remained stable. Data presented are means ± SEM; *p < 0.05.
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Fig2: Effect of vitamin D depletion ontibialis anteriororsoleus/body weight ratio. On the day of euthanasia, tibialis anterior (TA) (A) and soleus(B) of control and depleted rats were removed and weighed. TA or soleus/body weight ratio was calculated for each rat (n = 7 for control group and n = 9 for depleted group). TA/body weight ratio decreased in vitamin D-depleted old rats compared to control rats, whereas soleus/body weight ratio remained stable. Data presented are means ± SEM; *p < 0.05.

Mentions: Mean daily food intake throughout the experiment was equivalent between the two diet groups, except at week 20, i.e. food intake of vitamin D-depleted rats was slightly but significantly more important than in the control group (Figure 1A). Body weight of vitamin D-depleted rats increased throughout the experiment and became significantly different in comparison with their control counterparts after 13 weeks (Figure 1B). At the beginning of the experiment, body composition of D-depleted and control rat was similar (Figure 1C). In contrast, percent fat mass was significantly increased by 43% (p < 0.05) whereas percent lean mass was reduced by 12% (p < 0.001) in D-depleted rats compared to controls at the end of the experiment (Figure 1D). Moreover, D-depleted rats showed significantly greater variation in lean mass over the experimental period than controls (control group vs. depleted group: -2% vs. -9%, p < 0.05; Figure 1E). Fat mass variation was similar between the two groups but tended to be higher in vitamin D-depleted rats. Type II muscle mass was preferentially affected by vitamin D depletion, since TA/body weight ratio decreased in vitamin D-depleted old rats (-25%, p < 0.05, Figure 2A), whereas type I soleus/body weight ratio remained unchanged between the two groups (Figure 2B).Figure 1


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

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 - Nutr Metab (Lond) (2014)

Effect of vitamin D depletion ontibialis anteriororsoleus/body weight ratio. On the day of euthanasia, tibialis anterior (TA) (A) and soleus(B) of control and depleted rats were removed and weighed. TA or soleus/body weight ratio was calculated for each rat (n = 7 for control group and n = 9 for depleted group). TA/body weight ratio decreased in vitamin D-depleted old rats compared to control rats, whereas soleus/body weight ratio remained stable. Data presented are means ± SEM; *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4195890&req=5

Fig2: Effect of vitamin D depletion ontibialis anteriororsoleus/body weight ratio. On the day of euthanasia, tibialis anterior (TA) (A) and soleus(B) of control and depleted rats were removed and weighed. TA or soleus/body weight ratio was calculated for each rat (n = 7 for control group and n = 9 for depleted group). TA/body weight ratio decreased in vitamin D-depleted old rats compared to control rats, whereas soleus/body weight ratio remained stable. Data presented are means ± SEM; *p < 0.05.
Mentions: Mean daily food intake throughout the experiment was equivalent between the two diet groups, except at week 20, i.e. food intake of vitamin D-depleted rats was slightly but significantly more important than in the control group (Figure 1A). Body weight of vitamin D-depleted rats increased throughout the experiment and became significantly different in comparison with their control counterparts after 13 weeks (Figure 1B). At the beginning of the experiment, body composition of D-depleted and control rat was similar (Figure 1C). In contrast, percent fat mass was significantly increased by 43% (p < 0.05) whereas percent lean mass was reduced by 12% (p < 0.001) in D-depleted rats compared to controls at the end of the experiment (Figure 1D). Moreover, D-depleted rats showed significantly greater variation in lean mass over the experimental period than controls (control group vs. depleted group: -2% vs. -9%, p < 0.05; Figure 1E). Fat mass variation was similar between the two groups but tended to be higher in vitamin D-depleted rats. Type II muscle mass was preferentially affected by vitamin D depletion, since TA/body weight ratio decreased in vitamin D-depleted old rats (-25%, p < 0.05, Figure 2A), whereas type I soleus/body weight ratio remained unchanged between the two groups (Figure 2B).Figure 1

Bottom Line: Muscle repair depends on satellite cells whose pool size is diminished with aging.An unpaired student's t-test was performed to test the effect of the experimental conditions.Vitamin D deficiency could aggravate the age-related decrease in muscle regeneration capacity.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus