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Diet-Induced Vitamin D Deficiency Results in Reduced Skeletal Muscle Mitochondrial Respiration in C57BL/6J Mice
bioRxiv - Physiology Pub Date : 2020-05-16 , DOI: 10.1101/2020.05.15.098087
Stephen P. Ashcroft , Gareth Fletcher , Ashleigh M. Philp , Philip J. Atherton , Andrew Philp

Vitamin D deficiency is known to be 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 fed either a control (2,200 IU/kg) or a vitamin D deplete (0 IU/kg) diet for periods of 1-, 2- and 3-months. Skeletal muscle mitochondrial function and ADP sensitivity were assessed via high-resolution respirometry and mitochondrial protein content via immunoblotting. As a result of 3-month of diet-induced vitamin D deficiency, respiration supported via CI+IIP and ETC were 35% and 37% lower when compared to vitamin D replete mice (P < 0.05). Despite functional alterations, the protein expression of electron transfer chain subunits 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 function in C57BL/6J mice. Our data, when combined with previous in vitro observations, suggests that vitamin D mediated regulation of mitochondrial function may underlie the exacerbated muscle fatigue and performance deficits observed during vitamin D deficiency.

中文翻译:

饮食诱导的维生素D缺乏导致C57BL / 6J小鼠骨骼肌线粒体呼吸减少

维生素D缺乏症与骨骼肌肌病的症状有关,包括肌肉无力和疲劳。最近,与维生素D相关的代谢产物与骨骼肌内线粒体功能的维持有关。但是,目前的证据仅限于体外模型,饮食引起的维生素D缺乏对体内骨骼肌线粒体功能的影响很少受到关注。为了检查维生素D在体内维持线粒体功能中的作用,我们利用了饮食引起的C57BL / 6J小鼠维生素D缺乏症模型。给小鼠喂食对照(2,200 IU / kg)或贫维生素D(0 IU / kg)饮食,持续1、2、3个月。通过高分辨率呼​​吸测定法评估骨骼肌线粒体功能和ADP敏感性,并通过免疫印迹评估线粒体蛋白含量。由于饮食引起的维生素D缺乏症持续3个月,与补充维生素D的小鼠相比,通过CI + IIP和ETC支持的呼吸作用分别降低了35%和37%(P <0.05)。尽管功能发生了变化,但由于饮食干预,电子转移链亚基的蛋白表达仍保持不变(P> 0.05)。总之,我们报告了3个月的饮食诱导的维生素D缺乏症会降低C57BL / 6J小鼠的骨骼肌线粒体功能。我们的数据,加上以前的体外观察,
更新日期:2020-05-16
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