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Hypothesis: Obesity reduces Vitamin D production by repressing CYP2R1 gene in liver and fat tissue – July 2020

Obesity represses CYP2R1 , the vitamin D 25‐hydroxylase, in the liver and extrahepatic tissues

Journal of Bone and Mineral Research PLUS https://doi.org/10.1002/jbm4.10397
Mahmoud‐Sobhy Elkhwanky Outi Kummu Terhi T. Piltonen Johanna Laru Laure Morin‐Papunen Maija Mutikainen Pasi Tavi Jukka Hakkola

  • For years it had been believed that obese people store vitamin D in fatty tissue.
  • This study found that surgically removing fatty tissue in humans increases the activation of the CYP2R1 gene, which results in semi-activation of more Vitamin D
    • This could be the reason that more vitamin D appears to increase after weight loss, rather than the theory that fatty tissue stores the Vitamin D
  • But, fat surgery also decreases the amount of semi-activated VItamin D in the blood which is activated (CYP27B1)


Overview Obesity and Vitamin D contains the following summary


  • Normal weight     Obese     (50 ng = 125 nanomole)

CYP27B1 category listing contains the following

The CYP27B1 gene activates Vitamin D in the Kidney,    Skin,    Lungs,    Brain,   Eyes   Breasts   etc.
CYtochrome P450 family 27 subfamily B member 1    = 25-Hydroxyvitamin D3 1-alpha-hydroxylase

Vitamin D blood test misses CYP27B1 and other genes
in Visio for 2023

Items in both of the categories of Genetics AND Obesity

 Download the PDF from VitaminDWiki

Low plasma level of 25‐hydroxyvitamin D (25‐OH‐D), namely vitamin D deficiency, is associated with obesity and weight loss improves 25‐OH‐D status. However, the mechanism behind obesity‐induced vitamin D deficiency remains unclear. Here, we report that obesity suppresses the expression of cytochrome P450 (CYP) 2R1, the main vitamin D 25‐hydroxylase, in both mice and humans.

In humans, weight loss induced by gastric bypass surgery increased the expression of CYP2R1 in the subcutaneous adipose tissue suggesting recovery after the obesity‐induced suppression. At the same time, CYP27B1, the vitamin D 1α‐hydroxylase, was repressed by the weight loss. In a mouse (C57BL/6N) model of diet‐induced obesity, the plasma 25‐OH‐D was decreased. In accordance, the CYP2R1 expression was strongly repressed in the liver. Moreover, obesity repressed the expression of CYP2R1 in several extrahepatic tissues e.g. the kidney, brown adipose tissue and testis but not in the white adipose tissue. Obesity had a similar effect in both male and female mice. In mice, obesity repressed expression of the vitamin D receptor in brown adipose tissue. Obesity also upregulated the expression of the vitamin D receptor and CYP24A1 in the subcutaneous adipose tissue of a subset of mice; however, no effect was observed in the human subcutaneous adipose tissue.
In summary, we show that obesity affects CYP2R1 expression both in the mouse and human tissues. We suggest that in mouse the CYP2R1 repression in the liver plays an important role in obesity‐induced vitamin D deficiency.
Currently, it is unclear whether the CYP2R1 downregulation in extrahepatic tissues could contribute to the obesity‐induced low plasma 25‐OH‐D, however, this phenomenon may affect at least the local 25‐OH‐D concentrations.

Created by admin. Last Modification: Tuesday July 21, 2020 16:00:45 GMT-0000 by admin. (Version 6)

Attached files

ID Name Comment Uploaded Size Downloads
14062 Human fat gene changes.jpg admin 21 Jul, 2020 14:17 80.21 Kb 420
14061 Obesity represses CYP2R1.pdf PDF 2020 admin 21 Jul, 2020 14:17 3.42 Mb 410