The role of Vitamin D and the Vitamin D receptor in skeletal muscle function and exercise adaptation

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Ashcroft, Stephen Paul (2020). The role of Vitamin D and the Vitamin D receptor in skeletal muscle function and exercise adaptation. University of Birmingham. Ph.D.

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Abstract

Vitamin D deficiency remains prevalent throughout the world, with severe deficiencies resulting in skeletal muscle myopathies. Within skeletal muscle, a dynamic network of mitochondria exists primarily functioning to produce ATP via oxidative phosphorylation. Recent investigations have proposed that vitamin D related metabolites are able to modulate mitochondrial function within skeletal muscle cell lines and human populations with severe vitamin D deficiencies. Therefore, the aims of this thesis were to further explore the role of vitamin D related signalling via the VDR and diet-induced vitamin D deficiency in modulating skeletal muscle mitochondrial function. It was demonstrated that a reduction in the VDR significantly reduced mitochondrial respiration in the C2C12 skeletal muscle cell line without altering mitochondrial protein content. Furthermore, in vivo investigations revealed a reduction in skeletal muscle mitochondrial respiration following 3-months of diet-induced vitamin D deficiency in mice. Finally, we also demonstrated an impairment in voluntary wheel running performance and the subsequent adaptive response following diet-induced vitamin D deficiency in mice. In summary, this thesis contributes novel data towards the understanding of the role of the vitamin D and the VDR in modulating skeletal muscle mitochondrial function.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):