Diet-induced vitamin D deficiency reduces skeletal muscle mitochondrial respiration

in Journal of Endocrinology
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  • 1 School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
  • 2 MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Clinical, Metabolic and Molecular Physiology, University of Nottingham, Royal Derby Hospital Centre, Derby, UK
  • 3 Mitochondrial Metabolism and Ageing Laboratory, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
  • 4 St Vincent’s Clinical School, UNSW Medicine, UNSW Sydney, New South Wales, Australia
  • 5 Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
  • 6 ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia
  • 7 Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  • 8 UTS Centenary Centre for Inflammation, University Technology Sydney, New South Wales, Australia

Correspondence should be addressed to A Philp: a.philp@garvan.org.au
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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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