Decreased Serum 25-Hydroxyvitamin D in Aging Male Mice Is Associated With Reduced Hepatic Cyp2r1 Abundance

Roizen, Jeffrey D.; Casella, Alex; Lai, Meizan; Long, C. N. H.; Tara, Zahra; Caplan, Ilana; O'Lear, Lauren; Levine, Michael A.

doi:10.1210/en.2017-03028

Cited by 22 publications

(13 citation statements)

References 22 publications

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“…Roizen et al attributed this finding to a reduction in CYP2R1 activity in aging, since CYP2R1 mRNA and protein content in hepatic tissue of male mice progressively decreased from 26 to 39 and 49 weeks (one-way ANOVA, p = 0.0077). Moreover, the 25OHD3/VitD3 ratio was positively correlated with CYP2R1 mRNA and consistently declined with age [37].…”

Section: Liver and A New Life For Cyp2r1mentioning

confidence: 90%

An Update on Vitamin D Metabolism

Saponaro

Saba

Zucchi

2020

IJMS

191

150

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Vitamin D is a steroid hormone classically involved in the calcium metabolism and bone homeostasis. Recently, new and interesting aspects of vitamin D metabolism has been elucidated, namely the special role of the skin, the metabolic control of liver hydroxylase CYP2R1, the specificity of 1α-hydroxylase in different tissues and cell types and the genomic, non-genomic and epigenomic effects of vitamin D receptor, which will be addressed in the present review. Moreover, in the last decades, several extraskeletal effects which can be attributed to vitamin D have been shown. These beneficial effects will be here summarized, focusing on the immune system and cardiovascular system.

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Section: Liver and A New Life For Cyp2r1mentioning

confidence: 90%

An Update on Vitamin D Metabolism

Saponaro

Saba

Zucchi

2020

IJMS

191

150

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“…The hepatic CYP2R1 abundance has been reported to be decreased with age ( 15 ); however, the mechanism is not yet clear. Therefore, we compared the relative basal Cyp2r1 mRNA level in mice of different ages (control groups of the 4-, 8-, and 13-week experiments).…”

Section: Resultsmentioning

confidence: 99%

Streptozotocin-induced Diabetes Represses Hepatic CYP2R1 Expression but Induces Vitamin D 25-Hydroxylation in Male Mice

2022

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Vitamin D deficiency (i.e., low plasma 25-hydroxyvitamin D (25-OH-D)) associates with the prevalence of metabolic diseases including type 1 diabetes, however, the molecular mechanisms are incompletely understood. Recent studies have indicated that both fasting and metabolic diseases suppress the cytochrome P450 (CYP) 2R1, the major hepatic vitamin D 25-hydroxylase. We now specifically studied the effect of a mouse model of type 1 diabetes on the regulation of Cyp2r1 and vitamin D status. We show that streptozotocin-induced diabetes in mice suppresses the expression of the Cyp2r1 in the liver. While insulin therapy normalized the blood glucose levels in the diabetic mice, it did not rescue the diabetes-induced suppression of Cyp2r1. Similar regulation of Cyp2r1 was observed also in the kidney. Plasma 25-OH-D level was not decreased, and was, in contrast, higher after 4 and 8 weeks of diabetes. Furthermore, the vitamin D 25-hydroxylase activity was increased in the livers of the diabetic mice suggesting compensation of the Cyp2r1 repression by other vitamin D 25-hydroxylase enzymes. Cyp27b1, the vitamin D 1α-hydroxylase, expression in the kidney and the plasma 1α,25-dihydroxyvitamin D level were higher after 4 weeks of diabetes, while both were normalized after 13 weeks. In summary, these results indicate that in the mouse model of type 1 diabetes suppression of hepatic Cyp2r1 expression does not result in reduced hepatic vitamin D 25-hydroxylase activity and vitamin D deficiency. This may be due to induction of other vitamin D 25-hydroxylase enzymes in response to diabetes.

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“…However, recent studies suggest that both age and metabolism can modulate CYP27A activity. Aged humans and animals are characterized by a lower expression of CYP2R1 than their young counterparts and thus they are less responsive to vitamin D supplementation [86]. As vitamin D can be sequestered in adipose tissue [87], it is not surprising that nutrition and body composition also modulate CYP2R activity [87,88].…”

Section: Influence Of 25(oh)d In Pathological Conditionsmentioning

confidence: 99%

Vitamin D Metabolites: Analytical Challenges and Clinical Relevance

et al. 2022

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Recent research activities have provided new insights in vitamin D metabolism in various conditions. Furthermore, substantial progress has been made in the analysis of vitamin D metabolites and related biomarkers, such as vitamin D binding protein. Liquid chromatography tandem mass spectrometric (LC–MS/MS) methods are capable of accurately measuring multiple vitamin D metabolites in parallel. Nevertheless, only 25(OH)D and the biologically active form 1,25(OH)2D are routinely measured in clinical practice. While 25(OH)D remains the analyte of choice for the diagnosis of vitamin D deficiency, 1,25(OH)2D is only recommended in a few conditions with a dysregulated D metabolism. 24,25(OH)2D, free and bioavailable 25(OH)D, and the vitamin D metabolite ratio (VMR) have shown promising results, but technical pitfalls in their quantification, limited clinical data and the lack of reference values, impede their use in clinical practice. LC–MS/MS is the preferred method for the measurement of all vitamin D related analytes as it offers high sensitivity and specificity. In particular, 25(OH)D and 24,25(OH)2D can accurately be measured with this technology. When interpreted together, they seem to provide a functional measure of vitamin D metabolism beyond the analysis of 25(OH)D alone. The determination of VDBP, free and bioavailable 25(OH)D is compromised by unresolved analytical issues, lacking reference intervals and insufficient clinical data. Therefore, future research activities should focus on analytical standardization and exploration of their clinical value. This review provides an overview on established and new vitamin D related biomarkers including their pathophysiological role, preanalytical and analytical aspects, expected values, indications and influencing conditions.

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Decreased Serum 25-Hydroxyvitamin D in Aging Male Mice Is Associated With Reduced Hepatic Cyp2r1 Abundance

Cited by 22 publications

References 22 publications

An Update on Vitamin D Metabolism

An Update on Vitamin D Metabolism

Streptozotocin-induced Diabetes Represses Hepatic CYP2R1 Expression but Induces Vitamin D 25-Hydroxylation in Male Mice

Vitamin D Metabolites: Analytical Challenges and Clinical Relevance

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