Inhibition of Niemann-Pick C1-like protein 1 by ezetimibe reduces uptake of deuterium-labeled vitamin D in mice

Kiourtzidis, Mikis; Kühn, Julia; Schutkowski, Alexandra; Baur, Anja C.; Hirche, Frank; Stangl, Gabriele I.

doi:10.1016/j.jsbmb.2019.105504

Cited by 18 publications

(18 citation statements)

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“…Sample size was calculated using G*Power software (version 3.1.9.6) to determine statistically significant differences in the tissue levels of vitamin D 3 -d 3 . Recently published data on the importance of the NPC1L1 transporter for the uptake and tissue distribution of vitamin D in mice treated with ezetimibe [7] were used as a basis for sample size calculation. Using an estimated effect size of 3,76 (Cohen's d), a significance level of 5% and a power of 0.95, a minimum of 5 mice per group was considered to be a sufficient sample size.…”

Section: Animals and Feedingmentioning

confidence: 99%

“…Subsequently, mice aged 6 to 8 weeks were fed a standardized diet containing 25 µg/kg (1000 IU/kg) vitamin D 3 -d 3 (Sigma-Aldrich, Steinheim, Germany) as the only source of vitamin D for six weeks. This feeding period has been shown to be long enough to induce distinct changes in vitamin D metabolism [7]. The use of deuterated vitamin D ensures a closer tracking of ingested vitamin D and its metabolic route in the body.…”

Section: Animals and Feedingmentioning

confidence: 99%

“…Blood was collected in serum tubes (Sarstedt, Nümbrecht, Germany) for analyses of cholesterol, triglycerides, transaminases and vitamin D metabolites. As we recently demonstrated that liver, retroperitoneal adipose tissue, kidney and heart are the major tissues showing substantial quantities of vitamin D [7], we decided to use these tissues to analyze the concentrations of deuterium-labeled vitamin D 3 metabolites. The liver was additionally used for analyses of cholesterol and triglycerides.…”

Section: Sample Collectionmentioning

confidence: 99%

“…The concentrations of 7-DHC, vitamin D 3 -d 3 , and triple-deuterated 25-hydroxyvitamin D 3 (25(OH)D 3 -d 3 ) were quantified in serum and tissues by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample preparation and quantification of the sterols were performed as described recently [7]. Mass transitions were (as adducts of 4-phenyl-1,2,4-triazoline-3,5-dione; Sigma-Aldrich): 7-DHC 560 > 365, 7-fold deuterated 7-DHC 567 > 372, vitamin D 3 -d 3 563 > 301, 7-fold deuterated vitamin D 3 567 > 298, 25(OH)D 3 -d 3 579 > 301, and 6-fold deuterated 25(OH)D 3 582 > 298.…”

Section: Analysis Of 7-dehydrocholesterol and Vitamin D Metabolitesmentioning

confidence: 99%

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Vitamin D Status of Mice Deficient in Scavenger Receptor Class B Type 1, Cluster Determinant 36 and ATP-Binding Cassette Proteins G5/G8

et al. 2020

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Classical lipid transporters are suggested to modulate cellular vitamin D uptake. This study investigated the vitamin D levels in serum and tissues of mice deficient in SR-B1 (Srb1-/-), CD36 (Cd36-/-) and ABC-G5/G8 (Abcg5/g8-/-) and compared them with corresponding wild-type (WT) mice. All mice received triple-deuterated vitamin D3 (vitamin D3-d3) for six weeks. All knockout mice vs. WT mice showed specific alterations in their vitamin D concentrations. Srb1-/- mice had higher levels of vitamin D3-d3 in the serum, adipose tissue, kidney and heart, whereas liver levels of vitamin D3-d3 remained unaffected. Additionally, Srb1-/- mice had lower levels of deuterated 25-hydroxyvitamin D3 (25(OH)D3-d3) in the serum, liver and kidney compared to WT mice. In contrast, Cd36-/- and WT mice did not differ in the serum and tissue levels of vitamin D3-d3, but Cd36-/- vs. WT mice were characterized by lower levels of 25(OH)D3-d3 in the serum, liver and kidney. Finally, Abcg5/g8-/- mice tended to have higher levels of vitamin D3-d3 in the serum and liver. Major alterations in Abcg5/g8-/- mice were notably higher levels of 25(OH)D3-d3 in the serum and kidney, accompanied by a higher hepatic mRNA abundance of Cyp27a1 hydroxylase. To conclude, the current data emphasize the significant role of lipid transporters in the uptake, tissue distribution and activation of vitamin D.

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Section: Animals and Feedingmentioning

confidence: 99%

Section: Animals and Feedingmentioning

confidence: 99%

Section: Sample Collectionmentioning

confidence: 99%

Section: Analysis Of 7-dehydrocholesterol and Vitamin D Metabolitesmentioning

confidence: 99%

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Vitamin D Status of Mice Deficient in Scavenger Receptor Class B Type 1, Cluster Determinant 36 and ATP-Binding Cassette Proteins G5/G8

et al. 2020

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“…Mice that were fed diets containing 7-dehydrocholesterol or ergosterol showed significantly increased vitamin D stores in the liver and kidney, while having unchanged serum concentrations of 25(OH)D [17,18]. Additionally, mice that received ezetimibe, an inhibitor of the sterol transporter Niemann-Pick C1-like 1 protein, had markedly reduced vitamin D stores in the liver, kidney, adipose tissues and muscle, while the circulating concentrations of 25(OH)D had increased [19].…”

Section: Introductionmentioning

confidence: 99%

Markers Indicating Body Vitamin D Stores and Responses of Liver and Adipose Tissues to Changes in Vitamin D Intake in Male Mice

et al. 2020

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Circulating 25-hydroxyvitamin D (25(OH)D) is regarded as the most reliable biomarker of vitamin D status. However, limited data exist concerning the suitability of 25(OH)D as an indicator of body vitamin D stores and the ability of adipose tissue to mobilize vitamin D. In the first study, in which male mice received different vitamin D3 doses for three weeks, we found strong linear response relationships between vitamin D3 intake and levels of vitamin D3 in the plasma (p < 0.001), liver (p < 0.001) and adipose tissues (p < 0.001), and strong positive correlations between plasma and tissue stores of vitamin D3 (p < 0.001). Plasma levels of 25(OH)D3 and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) showed weak or no correlations with tissue vitamin D3 stores. Data from a second study demonstrate a strong and rapid response of plasma 25(OH)D3 in vitamin D3-treated mice with a low vitamin D status. Additionally, mice fed a vitamin D-free diet showed a strong and rapid decline in vitamin D3 in the liver, whereas the decline in different adipose tissues was distinctly lower than that in the liver. To conclude, tissue stores of vitamin D3 were best reflected by plasma vitamin D3. In contrast to the liver, adipose tissues responded less sensitively to an absence of vitamin D intake.

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Oral Intake of Lumisterol Affects the Metabolism of Vitamin D

Kotwan

Kühn

Baur

et al. 2021

Molecular Nutrition Food Res

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Scope: The treatment of food with ultraviolet-B (UV-B) light to increase the vitamin D content is accompanied by the formation of photoisomers, such as lumisterol 2 . The physiological impact of photoisomers is largely unknown. Methods and Results: Three groups of C57Bl/6 mice are fed diets containing 50 µg kg -1 deuterated vitamin D 3 with 0, 50 (moderate-dose) or 2000 µg kg -1 (high-dose) lumisterol 2 for four weeks. Considerable quantities of lumisterol 2 and vitamin D 2 are found in the plasma and tissues of mice fed with 2000 µg kg -1 lumisterol 2 but not in those fed 0 or 50 µg kg -1 lumisterol 2 . Mice fed with 2000 µg kg -1 lumisterol 2 showed strongly reduced deuterated 25-hydroxyvitamin D 3 (-50%) and calcitriol (-80%) levels in plasma, accompanied by downregulated mRNA abundance of cytochrom P450 (Cyp)27b1 and upregulated Cyp24a1 in the kidneys. Increased tissue levels of vitamin D 2 were also seen in mice in a second study that are kept on a diet with 0.2% UV-B exposed yeast versus those fed 0.2% untreated yeast containing iso-amounts of vitamin D 2 . Conclusion: High doses of lumisterol 2 can enter the body, induce the formation of vitamin D 2 , reduce the levels of 25(OH)D 3 and calcitriol and strongly impact the expression of genes involved in the degradation and synthesis of bioactive vitamin D.

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Inhibition of Niemann-Pick C1-like protein 1 by ezetimibe reduces uptake of deuterium-labeled vitamin D in mice

Cited by 18 publications

References 30 publications

Vitamin D Status of Mice Deficient in Scavenger Receptor Class B Type 1, Cluster Determinant 36 and ATP-Binding Cassette Proteins G5/G8

Vitamin D Status of Mice Deficient in Scavenger Receptor Class B Type 1, Cluster Determinant 36 and ATP-Binding Cassette Proteins G5/G8

Markers Indicating Body Vitamin D Stores and Responses of Liver and Adipose Tissues to Changes in Vitamin D Intake in Male Mice

Oral Intake of Lumisterol Affects the Metabolism of Vitamin D

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