Modeling vitamin D insufficiency and moderate deficiency in adult mice via dietary cholecalciferol restriction

Abstract

Purpose We sought to develop and characterize a model of human vitamin D nutritional insufficiency/deficiency in the adult mouse, which could have broad utility in examining health consequences of this common condition. Methods Adult mice were fed diets containing cholecalciferol contents of 0.05IU/g, 0.25IU/g, 0.5IU/g or 1.5IU/g for four months. We studied induction of steady-state vitamin D insufficiency, and its consequences on primary cholecalciferol metabolite levels, calcium homeostasis, parathyroid physiology, and bone morphology. Results All diets were well tolerated, without adverse effects on body weight. Diets containing 0.05IU/g and 0.25 IU/g cholecalciferol significantly lowered serum 25-hydroxyvitamin D levels (median 25OHD, 10.5 ng/ml, and 21.6 ng/ml, respectively), starting as early as 1 month following initiation of the diets, maintained through the 4-month experimental period. The 0.05IU/g diet significantly decreased 1,25-dihydroxyvitamin D (1,25OH2D) levels (median, 78 pg/ml). Despite these decreased 25OHD and 1,25OH2D levels, the diets did not alter parathyroid gland morphology or parathyroid cell proliferation. There were no statistical differences in the serum total calcium and serum PTH levels among the various dietary groups. Furthermore, the 0.05IU/g diet did not cause any alterations in the cortical and trabecular bone morphology, as determined by microCT. Conclusions The dietary manipulations yielded states of vitamin D insufficiency or modest deficiency in adult mice, with no overtly detectable impact on parathyroid and bone physiology, and calcium homeostasis. This model system may be of value to study health effects of vitamin D insufficiency/deficiency especially on extraskeletal phenotypes such as cancer susceptibility or immune function.

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

“…With regards to other serum markers, Belenchia et al reported changes in serum calcium levels in vitamin D deficient mice, which was not observed in this study, our previous study [ 47 ], or by Mallya et al [ 63 ]. Likewise, Belenchia et al was the only study to report significant differences in PTH concentrations; however, intact PTH was trending towards elevation in our vitamin D insufficient mice (p=0.10), and our study may have been insufficiently powered to observe this.…”

“…Our study also confirms the findings that altering vitamin D supplementation results in a rapid shift (both depletion and repletion) in serum 25-OH vitamin D levels (within 2 weeks) that is sustained relative to the amount of supplementation [ 33 , 47 , 63 ]. Our 12-month study was approximately 6 weeks longer than Belenchia et al [ 33 ], which was performed in female mice, and together these studies demonstrate little to no impact of gender on the relationship between vitamin D supplementation and serum 25-OH vitamin D concentration.…”

Bile acid composition regulates the manganese transporter Slc30a10 in intestine

“…The vitamin D level was adjusted to minimize the contribution of dietary vitamin D to VDR signaling, which might interfere with the effects of LCA. This dose of vitamin D has been previously shown to cause no significant changes in body weight, serum calcium, serum parathyroid hormone, cortical or trabecular bone density, or parathyroid gland morphology, even after 4 months on the diet (86,87). We observed no overt defects in the mice after 3 days on this diet.…”

Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption

“…The Ch and Ch-D diets were purchased from Purina Mills LabDiet. Levels of dietary D3 used in deficient diets are high enough to prevent physiologically relevant changes in levels of serum calcium, serum phosphate, or parathyroid hormone ( Anderson et al, 2007 ; Harnack et al, 2011 ; Mallya et al, 2016 ). Animals (for mice and rats, see Table 2 ) used in all treatment studies were maintained on either standard rodent Ch (RMH 3000, Purina Mills LabDiet), the HF diet, or the HF-D diet ( Table 1 ).…”