Chronic vitamin D insufficiency impairs physical performance in C57BL/6J mice

Abstract

Vitamin D insufficiency (serum 25-OH vitamin D < 30 ng/ml) affects 70-80% of the general population, yet the long-term impacts on physical performance and the progression of sarcopenia are poorly understood. We therefore followed 6-month-old male C57BL/6J mice (n=6) consuming either sufficient (STD, 1000 IU) or insufficient (LOW, 125 IU) vitamin D3/kg chow for 12 months (equivalent to 20-30 human years). LOW supplemented mice exhibited a rapid decline of serum 25-OH vitamin D levels by two weeks that remained between 11-15 ng/mL for all time points thereafter. After 12 months LOW mice displayed worse grip endurance (34.6 ± 14.1 versus 147.5 ± 50.6 seconds, p=0.001), uphill sprint speed (16.0 ± 1.0 versus 21.8 ± 2.4 meters/min, p=0.0007), and stride length (4.4 ± 0.3 versus 5.1 ± 0.3, p=0.002). LOW mice also showed less lean body mass after 8 months (57.5% ± 5.1% versus 64.5% ± 4.0%, p=0.023), but not after 12 months of supplementation, as well as greater protein expression of atrophy pathway gene atrogin‑1. Additionally, microRNA sequencing revealed differential expression of mIR‑26a in muscle tissue of LOW mice. These data suggest chronic vitamin D insufficiency may be an important factor contributing to functional decline and sarcopenia.

Diet-Induced Vitamin D Deficiency Results in Reduced Skeletal Muscle Mitochondrial Respiration in C57BL/6J Mice

“…These effects are not mediated by alterations in mitochondrial protein content suggesting vitamin D deficiency directly effects the mitochondrial respiratory machinery. Similar to others, we observed minimal differences in body composition following 3-months of diet-induced vitamin D deficiency in male C57BL/6J mice [19 37]. Finally our data provides evidence that vitamin D status is an important determinant of skeletal muscle mitochondrial function in vivo thereby supporting previous in vitro observations.…”

“…In addition, we also sought to determine the effects of diet-induced vitamin D deficiency upon body composition within C57BL/6J mice. Previously, no differences in body weight and lean mass were observed following 12-months of diet-induced deficiency in male C57BL/6J mice [19]. In female mice however, 12-months of diet-induced vitamin D deficiency resulted in reductions in body weight, lean mass and fat mass [35].…”

“…This may in part be driven by the fact we also observed an increase in lean mass as a percentage of body weight following 1-month of diet-induced deficiency. Despite minimal differences in body composition, previous data suggests that vitamin D deficiency impairs physical function in mice [15 19]. Therefore, functional measures of muscle performance may be more relevant to assess the effects of vitamin D deficiency within skeletal muscle.…”

“…However, despite the administration of this rescue diet, mice still display reduced grip strength and an increase in Myostatin gene expression [15], a known negative regulator of muscle mass [18]. Similarly, mice fed this diet chronically (8-12 months) show similar impairments in physical performance including; reduced grip endurance, sprint speed and stride length [19].…”

“…In humans, the supplementation of vitamin D within a cohort of severely deficient individuals resulted in a reduced phosphocreatine (PCr) recovery time, as measured non-invasively by 31-phosphorous magnetic resonance spectroscopy (31-P MRS) [20]. Whilst skeletal muscle mitochondrial content seems to remain unchanged following diet-induced vitamin D deficiency in mice [19], the functional characteristics of the mitochondria remain largely underexplored. Therefore, we aimed to determine the effects of diet-induced vitamin D deficiency upon skeletal muscle mitochondrial function in C57BL/6J mice.…”