University of Oulu

Elkhwanky, M.‐S., Kummu, O., Piltonen, T.T., Laru, J., Morin‐Papunen, L., Mutikainen, M., Tavi, P. and Hakkola, J. (2020), Obesity Represses CYP2R1, the Vitamin D 25‐Hydroxylase, in the Liver and Extrahepatic Tissues. JBMR Plus, 4: e10397.

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

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Author: Elkhwanky, Mahmoud‐Sobhy1,2,3; Kummu, Outi1,2,3; Piltonen, Terhi T.4;
Organizations: 1Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, Oulu, Finland
2Biocenter Oulu, University of Oulu, Oulu, Finland
3Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
4Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
5A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.9 MB)
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Language: English
Published: John Wiley & Sons, 2020
Publish Date: 2020-11-27


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 s.c. 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, 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 s.c. adipose tissue of a subset of mice; however, no effect was observed in the human s.c. 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.

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Series: JBMR plus
ISSN: 2473-4039
ISSN-E: 2473-4039
ISSN-L: 2473-4039
Volume: 4
Issue: 11
Article number: e10397
DOI: 10.1002/jbm4.10397
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: The study was financially supported by grants from the Academy of Finland (grants 286743 and 323706 to JH; 315921 and 321763 to TTP) and the Diabetes Research Foundation. We thank Ritva Tauriainen and Elina Huikari for their skillful technical help.
Academy of Finland Grant Number: 286743
Detailed Information: 286743 (Academy of Finland Funding decision)
323706 (Academy of Finland Funding decision)
315921 (Academy of Finland Funding decision)
321763 (Academy of Finland Funding decision)
Copyright information: © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.