Journal
ENDOCRINE RESEARCH
Volume 41, Issue 4, Pages 290-299Publisher
TAYLOR & FRANCIS INC
DOI: 10.3109/07435800.2016.1141937
Keywords
Animal diet; parathyroid; vitamin D; 25-hydroxyvitamin D
Categories
Funding
- National Institutes of Health [R01DK066411, R03DE022598]
- Murray-Heilig Fund in Molecular Medicine
- American Institute of Cancer Research grant [10A046]
- UCLA School of Dentistry
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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 0.05 IU/g, 0.25 IU/g, 0.5 IU/g or 1.5 IU/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 0.05 IU/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 one month following initiation of the diets, maintained through the four-month experimental period. The 0.05 IU/g diet significantly decreased 1,25-dihydroxyvitamin D (1,25OH(2)D) levels (median, 78 pg/ml). Despite these decreased 25OHD and 1,25OH(2)D 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 0.05 IU/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.
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