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Diet-induced vitamin D deficiency reduces skeletal muscle mitochondrial respiration

Abstract

Vitamin D deficiency is associated with symptoms of skeletal muscle myopathy including muscle weakness and fatigue. Recently, vitamin D-related metabolites have been linked to the maintenance of mitochondrial function within skeletal muscle. However, current evidence is limited to in vitro models and the effects of diet-induced vitamin D deficiency upon skeletal muscle mitochondrial function in vivo have received little attention. In order to examine the role of vitamin D in the maintenance of mitochondrial function in vivo, we utilised an established model of diet-induced vitamin D deficiency in C57BL/6J mice. Mice were either fed a control diet (2200 IU/kg i.e. vitamin D replete) or a vitamin D-deplete (0 IU/kg) diet for periods of 1, 2 and 3 months. Gastrocnemius muscle mitochondrial function and ADP sensitivity were assessed via high-resolution respirometry and mitochondrial protein content via immunoblotting. As a result of 3 months of diet-induced vitamin D deficiency, respiration supported via complex I + II (CI + IIP) and the electron transport chain (ETC) were 35 and 37% lower when compared to vitamin D-replete mice (P < 0.05). Despite functional alterations, citrate synthase activity, AMPK phosphorylation, mitofilin, OPA1 and ETC subunit protein content remained unchanged in response to dietary intervention (P > 0.05). In conclusion, we report that 3 months of diet-induced vitamin D deficiency reduced skeletal muscle mitochondrial respiration in C57BL/6J mice. Our data, when combined with previous in vitro observations, suggest that vitamin D-mediated regulation of mitochondrial function may underlie the exacerbated muscle fatigue and performance deficits observed during vitamin D deficiency.

Type Journal
ISBN 1479-6805 (Electronic) 0022-0795 (Linking)
Authors Ashcroft, S. P.; Fletcher, G.; Philp, A. M.; Jenkinson, C.; Das, S.; Hansbro, P. M.; Atherton, P. J.; Philp, A.
Responsible Garvan Author Dr Andy Philp
Publisher Name JOURNAL OF ENDOCRINOLOGY
Published Date 2021-05-31
Published Volume 249
Published Issue 2
Published Pages 113-124
Status Published in-print
DOI 10.1530/JOE-20-0233
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/33862598