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Livers of obese mice had less CYP2R1 needed to activate Vitamin D – Jan 2019

Obesity Decreases Hepatic 25‐Hydroxylase Activity Causing Low Serum 25‐Hydroxyvitamin D

Journal of Bone Mineral Research https://doi.org/10.1002/jbmr.3686
Jeffrey D Roizen Caela Long Alex Casella Lauren O'Lear Ilana Caplan Meizan Lai Issac Sasson Ravinder Singh Andrew J Makowski … See all authors

VitaminDWiki

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Genetics category listing contains the following

234 articles in the Genetics category

see also 265 articles in Vitamin D Receptor, 98 articles in Vitamin D Binding Protein

Vitamin D blood test misses a lot
Blood Test Misses a lot (VDW 3439)

  • Snapshot of the literature by VitaminDWiki - (subject to many future developments)
  • Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, andi in 2017 is speculated to be 90%
  • Note: Good results from a blood test (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
  • A Vitamin D test in cells appears feasible (personal communication)
    However test results would vary in each tissue due to multiple genes
  • Good clues that Vitamin D is being restricted from getting to the cells
    1) A vitamin D-related health problem runs in the family
       especially if it is one of 47+ diseases related to Vitamin D Receptor
    2) Slightly increasing Vitamin D show benefits (even if conventional Vitamin D test shows an increase)
    3) Vitamin D Receptor test (<$30) scores are difficult to understand in 2016
        easier to understand the VDR 23andMe test results analyzed by FoundMyFitness in 2018
    4) Back Pain
        probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
          The founder of VitaminDWiki took action with clues #3&4

Overview Obesity and Vitamin D contains the following summary

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  • Normal weight     Obese     (50 ng = 125 nanomole)

 Download the PDF from Sci-Hub via VitaminDWiki
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Normal vitamin D homeostasis is critical for optimal health; nevertheless, vitamin D deficiency is a worldwide public health problem. Vitamin D insufficiency is most commonly due to inadequate cutaneous synthesis of cholecalciferol and/or insufficient intake of vitamin D, but can also arise as a consequence of pathological states such as obesity. Serum concentrations of 25(OH)D (calcidiol) are low in obesity, and fail to increase appropriately after vitamin D supplementation.

Although sequestration of vitamin D in adipose tissues or dilution of ingested or cutaneously synthesized vitamin D in the large fat mass of obese patients has been proposed to explain these findings, here we investigate the alternative mechanism that reduced capacity to convert parent vitamin D to 25(OH)D due to decreased expression of CYP2R1, the principal hepatic vitamin D 25‐hydroxylase.

To test this hypothesis, we isolated livers from female mice of 6 to 24 weeks of age, weaned onto either a normal chow diet or a high‐fat diet, and determined the abundance of Cyp2r1 mRNA using digital droplet‐quantitative PCR. We observed a significant (p < 0.001) decrease in Cyp2r1 mRNA in the liver of high‐fat diet–fed mice relative to lean‐chow–fed female mice. Moreover, there was a significant (p < 0.01) relationship between levels of Cyp2r1 mRNA and serum 25(OH)D concentrations as well as between Cyp2R1 mRNA and the ratio of circulating 25(OH)D3 to cholecalciferol (p < 0.0001).
Using linear regression we determined a curve with 25(OH)D3/cholecalciferol versus normalized Cyp2R1 mRNA abundance with an R2 value of 0.85. Finally, we performed ex vivo activity assays of isolated livers and found that obese mice generated significantly less 25(OH)D3 than lean mice (p < 0.05). Our findings indicate that expression of CYP2R1 is reduced in obesity and accounts in part for the decreased circulating 25(OH)D.

Created by admin. Last Modification: Friday February 22, 2019 15:07:59 GMT-0000 by admin. (Version 6)

Attached files

ID Name Comment Uploaded Size Downloads
11443 Obese mice F4.jpg admin 22 Feb, 2019 14:35 17.09 Kb 7
11442 Obese mice.pdf PDF 2019 admin 22 Feb, 2019 14:35 680.67 Kb 5
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