Differential effects of vitamin D 3 vs vitamin D 2 on cellular uptake, tissue distribution and activation of vitamin D in mice and cells

• Published in: The Journal of steroid biochemistry and molecular biology 2020-11, Vol.204, p.105768
• Main Authors: Baur, Anja C, Brandsch, Corinna, Steinmetz, Benita, Schutkowski, Alexandra, Wensch-Dorendorf, Monika, Stangl, Gabriele I
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport; Cell Line, Tumor; Cholecalciferol - pharmacokinetics; Cytochrome P-450 Enzyme System - genetics; Ergocalciferols - pharmacokinetics; Humans; Kidney - metabolism; Liver - metabolism; Male; Mice, Inbred C57BL; Tissue Distribution; Vitamin D Deficiency - metabolism; Vitamins - pharmacokinetics
• ISSN: 1879-1220
• DOI: 10.1016/j.jsbmb.2020.105768

To combat vitamin D deficiency, vitamin D and vitamin D are commonly used as a supplement or to fortify food sources. Human data show that the response of 25-hydroxyvitamin D (25(OH)D) to supplementation with vitamin D is higher than to vitamin D . To elucidate the metabolic route of both vitamers, we conducted a study with vitamin D-depleted mice, which were allotted into three groups (n = 12) and received equal doses of either deuterated vitamin D , deuterated vitamin D or both for 4 weeks. To further investigate the hepatic uptake and hydroxylation of both D-vitamers to 25(OH)D, we conducted cell culture experiments with murine and human hepatoma cells (Hepa1-6 and HepG2). The vitamin D metabolite concentrations in serum, tissues and cells were analyzed by LC-MS/MS or ELISA. In mice, vitamin D resulted in lower serum and tissue concentrations of vitamin D (P < 0.001) than vitamin D , while the group which received both D-vitamers showed values in between. Interestingly, vitamin D fed mice had 1.9-times and 2.9-times higher serum concentrations of total and free 25(OH)D (P < 0.001) than mice fed vitamin D , while the concentration of 1,25-dihydroxyvitamin D (1,25(OH) D) was 1.8-times lower (P < 0.001). The gene and protein expression of enzymes, involved in the hydroxylation and renal uptake of vitamin D remained largely unaffected by the D-vitamer. In contrast to the mice data, hepatoma cells preferred vitamin D for 25-hydroxylation over vitamin D (P < 0.001). In general, the formation of 25(OH)D was much more pronounced in human than in murine hepatoma cells (P < 0.001). To conclude, in contrast to humans, vitamin D was more efficient in increasing 25(OH)D than vitamin D in mice, although this difference was not caused by a preferential hydroxylation of vitamin D in the liver. The metabolic routes of D and D in mice differ, showing lower circulating 1,25(OH) D and tissue vitamin D concentrations in D - than in D -fed mice.