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Dose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells.

ABSTRACT: Fat infiltration within muscle is one of a number of features of vitamin D deficiency, which leads to a decline in muscle functionality. The origin of this fat is unclear, but one possibility is that it forms from myogenic precursor cells present in the muscle, which transdifferentiate into mature adipocytes. The current study examined the effect of the active form of vitamin D?, 1,25-dihydroxyvitamin D? (1,25(OH)?D?), on the capacity of the C2C12 muscle cell line to differentiate towards the myogenic and adipogenic lineages. Cells were cultured in myogenic or adipogenic differentiation media containing increasing concentrations (0, 10?¹³, 10?¹¹, 10??, 10?? or 10?? ?M) of 1,25(OH)?D? for up to 6 days and markers of muscle and fat development measured. Mature myofibres were formed in both adipogenic and myogenic media, but fat droplets were only observed in adipogenic media. Relative to controls, low physiological concentrations (10?¹³ and 10?¹¹ ?M) of 1,25(OH)?D3 increased fat droplet accumulation, whereas high physiological (10?? ?M) and supraphysiological concentrations (?10?? ?M) inhibited fat accumulation. This increased accumulation of fat with low physiological concentrations (10?¹³ and 10?¹¹ ?M) was associated with a sequential up-regulation of PPAR?2 (PPARG) and FABP4 mRNA, indicating formation of adipocytes, whereas higher concentrations (?10?? ?M) reduced all these effects, and the highest concentration (10?? ?M) appeared to have toxic effects. This is the first study to demonstrate dose-dependent effects of 1,25(OH)?D? on the transdifferentiation of muscle cells into adipose cells. Low physiological concentrations (possibly mimicking a deficient state) induced adipogenesis, whereas higher (physiological and supraphysiological) concentrations attenuated this effect.

SUBMITTER: Ryan KJ

PROVIDER: S-EPMC3600570 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Dose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells.

Ryan Kevin J P KJ Daniel Zoe C T R ZC Craggs Lucinda J L LJ Parr Tim T Brameld John M JM

The Journal of endocrinology 20130401 1

Fat infiltration within muscle is one of a number of features of vitamin D deficiency, which leads to a decline in muscle functionality. The origin of this fat is unclear, but one possibility is that it forms from myogenic precursor cells present in the muscle, which transdifferentiate into mature adipocytes. The current study examined the effect of the active form of vitamin D₃, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), on the capacity of the C2C12 muscle cell line to differentiate towards the my ...[more]

PMID: 23328072

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Project description:Skeletal muscle function is highly dependent on the ability to regenerate, however, during ageing or disease, the proliferative capacity is reduced, leading to loss of muscle function. We have previously demonstrated the presence of vitamin K2 in bovine skeletal muscles, but whether vitamin K has a role in muscle regulation and function is unknown. In this study, we used primary bovine skeletal muscle cells, cultured in monolayers in vitro, to assess a potential effect of vitamin K2 (MK-4) during myogenesis of muscle cells. Cell viability experiments demonstrate that the amount of ATP produced by the cells was unchanged when MK-4 was added, indicating viable cells. Cytotoxicity analysis show that MK-4 reduced the lactate dehydrogenase (LDH) released into the media, suggesting that MK-4 was beneficial to the muscle cells. Cell migration, proliferation and differentiation was characterised after MK-4 incubation using wound scratch analysis, immunocytochemistry and real-time PCR analysis. Adding MK-4 to the cells led to an increased muscle proliferation, increased gene expression of the myogenic transcription factor myod as well as increased cell migration. In addition, we observed a reduction in the fusion index and relative gene expression of muscle differentiation markers, with fewer complex myotubes formed in MK-4 stimulated cells compared to control cells, indicating that the MK-4 plays a significant role during the early phases of muscle proliferation. Likewise, we see the same pattern for the relative gene expression of collagen 1A, showing increased gene expression in proliferating cells, and reduced expression in differentiating cells. Our results also suggest that MK-4 incubation affect low density lipoprotein receptor-related protein 1 (LRP1) and the low-density lipoprotein receptor (LDLR) with a peak in gene expression after 45 min of MK-4 incubation. Altogether, our experiments show that MK-4 has a positive effect on muscle cell migration and proliferation, which are two important steps during early myogenesis.

Dataset Information

Dose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells.

Publications

Dose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells.

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