Diet-induced vitamin D deficiency reduces skeletal muscle mitochondrial respiration

in Journal of Endocrinology
Authors:
Stephen P Ashcroft School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Clinical, Metabolic and Molecular Physiology, University of Nottingham, Royal Derby Hospital Centre, Derby, UK
Mitochondrial Metabolism and Ageing Laboratory, Garvan Institute of Medical Research, Sydney, New South Wales, Australia

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Gareth Fletcher Mitochondrial Metabolism and Ageing Laboratory, Garvan Institute of Medical Research, Sydney, New South Wales, Australia

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Ashleigh M Philp Mitochondrial Metabolism and Ageing Laboratory, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
St Vincent’s Clinical School, UNSW Medicine, UNSW Sydney, New South Wales, Australia

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Carl Jenkinson Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia

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Shatarupa Das Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
UTS Centenary Centre for Inflammation, University Technology Sydney, New South Wales, Australia

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Philip M Hansbro Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
UTS Centenary Centre for Inflammation, University Technology Sydney, New South Wales, Australia

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Philip J Atherton MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Clinical, Metabolic and Molecular Physiology, University of Nottingham, Royal Derby Hospital Centre, Derby, UK

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Andrew Philp Mitochondrial Metabolism and Ageing Laboratory, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
St Vincent’s Clinical School, UNSW Medicine, UNSW Sydney, New South Wales, Australia

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Correspondence should be addressed to A Philp: a.philp@garvan.org.au
DOI:
https://doi.org/10.1530/JOE-20-0233
Volume/Issue:
Volume 249: Issue 2
Article Type:
Research Article
Page Range:
113–124
Online Publication Date:
May 2021
Copyright:
© 2021 Society for Endocrinology 2021
Restricted access
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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.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2021 Society for Endocrinology 2021
Page(s):
12
Article Type:
Research Article
Received Date:
17 Feb 2021
Accepted Date:
09 Mar 2021
Print Publication Date:
01 May 2021
Online Publication Date:
May 2021
Keywords:
skeletal muscle; vitamin D; mitochondria

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