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 0.05 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 (1,25OH₂D) 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 0.05 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.

KEYWORDS:

• Animal diet
• parathyroid
• vitamin D
• 25-hydroxyvitamin D

Supplemental data

Supplemental data for this article can be accessed at www.tandfonline.com/ierc.

Acknowledgments

The authors thank Dr Thomas Carpenter (Yale University, New Haven, CT) for performing assays of serum 1,25OH₂D.

SMM and AA designed research; SMM, KRC, EAS, FFY, HQT, KS, and EA conducted research; SMM, KRC, EAS, FFY, HQT, KS, EA, ST and AA analyzed data; and SMM and AA wrote the paper. SMM and AA had primary responsibility for final content. All authors read and approved the final manuscript.

Declaration of interest

The authors do not have any conflicts of interest.

Funding

The research reported in this publication was supported by the National Institutes of Health under award numbers R01DK066411 (AA) and R03DE022598 (SM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This study was supported in part by the Murray-Heilig Fund in Molecular Medicine (AA), by the American Institute of Cancer Research grant 10A046 (SM), and by a seed grant from the UCLA School of Dentistry (SM).

Additional information

Funding

The research reported in this publication was supported by the National Institutes of Health under award numbers R01DK066411 (AA) and R03DE022598 (SM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This study was supported in part by the Murray-Heilig Fund in Molecular Medicine (AA), by the American Institute of Cancer Research grant 10A046 (SM), and by a seed grant from the UCLA School of Dentistry (SM).