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Expression of Vitamin D Receptor Pathway Genes in Subcutaneous Adipose Tissue of Obese Individuals

Introduction: Vitamin D deficiency is a substantial comorbidity in 50% of pediatric patients and is linked with poorer health outcomes in children. Vitamin D levels are also shown to be inversely related to BMI. Therefore, there are many more children with low vitamin D levels due to the increasing...

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Autores principales: Ginnard, Olivia Z B, Sisley, Stephanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090667/
http://dx.doi.org/10.1210/jendso/bvab048.1342
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author Ginnard, Olivia Z B
Sisley, Stephanie
author_facet Ginnard, Olivia Z B
Sisley, Stephanie
author_sort Ginnard, Olivia Z B
collection PubMed
description Introduction: Vitamin D deficiency is a substantial comorbidity in 50% of pediatric patients and is linked with poorer health outcomes in children. Vitamin D levels are also shown to be inversely related to BMI. Therefore, there are many more children with low vitamin D levels due to the increasing prevalence of pediatric obesity. Pediatric patients with obesity and vitamin D deficiency also have a uniquely increased risk of metabolic syndrome, as compared to their lean peers. Measured levels of vitamin D correlate with other physiological markers of vitamin D effects in lean individuals but not obese individuals. It is possible that vitamin D levels reflect a storage form of vitamin D rather than a true reflection of vitamin D action in the body in this particular population. The aim of this study was to provide foundational knowledge to understand if expression of vitamin D receptor (VDR)-target genes may be used as a reference standard for vitamin D status in the body. Methods: We performed a secondary analysis of samples obtained from 33 obese adolescents that were consented under a past IRB-approved protocol. They were between the ages of 13 to 18 years that underwent bariatric surgery between 2004 and 2019. Data comprised of age, gender, race/ethnicity, and BMI. Samples collected included blood and subcutaneous adipose tissue. The tissue was analyzed via Real Time-PCR to obtain quantitative levels of VDR-target gene expression, which included PPARg, TLR4, THBD, CYP24A1, and VDR. Gene expression levels were normalized to the average of two housekeeping genes, GAPDH and RPLPO. Blood samples provided vitamin D levels (serum 25(OH)D). Results: VDR-target gene expression was significantly correlated between THBD, VDR, and TLR4 (p <0.05), and PPARg with THBD and TLR4 (p <0.05). There was no correlation observed between CYP24A1 gene expression and the other genes that were evaluated (p >0.05). PPARg, THBD, TLR4, CYP24A1, and VDR gene expression levels did not correlate with circulating serum 25(OH)D levels (p >0.05). Conclusion: These preliminary findings suggest that VDR-target gene expression correlates with each other but not with circulating serum 25(OH)D levels. This discrepancy supports that 25(OH)D levels do not indicate levels of vitamin D action and may not be an appropriate indicator of vitamin D deficiency in the obese population. Also, the observed CYP24A1 gene expression was limited in subcutaneous adipose tissue yet expression was seen in multiple other VDR-target genes. This emphasizes the tissue-specific nature of gene regulation of vitamin D. Further work should investigate VDR-target gene expression levels across multiple tissues of obese individuals to determine if markers of vitamin D action in one tissue are reflective of action across the body. This study may provide the first step in determining a new and more accurate biomarker for vitamin D deficiency and treatment in obesity.
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spelling pubmed-80906672021-05-12 Expression of Vitamin D Receptor Pathway Genes in Subcutaneous Adipose Tissue of Obese Individuals Ginnard, Olivia Z B Sisley, Stephanie J Endocr Soc Pediatric Endocrinology Introduction: Vitamin D deficiency is a substantial comorbidity in 50% of pediatric patients and is linked with poorer health outcomes in children. Vitamin D levels are also shown to be inversely related to BMI. Therefore, there are many more children with low vitamin D levels due to the increasing prevalence of pediatric obesity. Pediatric patients with obesity and vitamin D deficiency also have a uniquely increased risk of metabolic syndrome, as compared to their lean peers. Measured levels of vitamin D correlate with other physiological markers of vitamin D effects in lean individuals but not obese individuals. It is possible that vitamin D levels reflect a storage form of vitamin D rather than a true reflection of vitamin D action in the body in this particular population. The aim of this study was to provide foundational knowledge to understand if expression of vitamin D receptor (VDR)-target genes may be used as a reference standard for vitamin D status in the body. Methods: We performed a secondary analysis of samples obtained from 33 obese adolescents that were consented under a past IRB-approved protocol. They were between the ages of 13 to 18 years that underwent bariatric surgery between 2004 and 2019. Data comprised of age, gender, race/ethnicity, and BMI. Samples collected included blood and subcutaneous adipose tissue. The tissue was analyzed via Real Time-PCR to obtain quantitative levels of VDR-target gene expression, which included PPARg, TLR4, THBD, CYP24A1, and VDR. Gene expression levels were normalized to the average of two housekeeping genes, GAPDH and RPLPO. Blood samples provided vitamin D levels (serum 25(OH)D). Results: VDR-target gene expression was significantly correlated between THBD, VDR, and TLR4 (p <0.05), and PPARg with THBD and TLR4 (p <0.05). There was no correlation observed between CYP24A1 gene expression and the other genes that were evaluated (p >0.05). PPARg, THBD, TLR4, CYP24A1, and VDR gene expression levels did not correlate with circulating serum 25(OH)D levels (p >0.05). Conclusion: These preliminary findings suggest that VDR-target gene expression correlates with each other but not with circulating serum 25(OH)D levels. This discrepancy supports that 25(OH)D levels do not indicate levels of vitamin D action and may not be an appropriate indicator of vitamin D deficiency in the obese population. Also, the observed CYP24A1 gene expression was limited in subcutaneous adipose tissue yet expression was seen in multiple other VDR-target genes. This emphasizes the tissue-specific nature of gene regulation of vitamin D. Further work should investigate VDR-target gene expression levels across multiple tissues of obese individuals to determine if markers of vitamin D action in one tissue are reflective of action across the body. This study may provide the first step in determining a new and more accurate biomarker for vitamin D deficiency and treatment in obesity. Oxford University Press 2021-05-03 /pmc/articles/PMC8090667/ http://dx.doi.org/10.1210/jendso/bvab048.1342 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Pediatric Endocrinology
Ginnard, Olivia Z B
Sisley, Stephanie
Expression of Vitamin D Receptor Pathway Genes in Subcutaneous Adipose Tissue of Obese Individuals
title Expression of Vitamin D Receptor Pathway Genes in Subcutaneous Adipose Tissue of Obese Individuals
title_full Expression of Vitamin D Receptor Pathway Genes in Subcutaneous Adipose Tissue of Obese Individuals
title_fullStr Expression of Vitamin D Receptor Pathway Genes in Subcutaneous Adipose Tissue of Obese Individuals
title_full_unstemmed Expression of Vitamin D Receptor Pathway Genes in Subcutaneous Adipose Tissue of Obese Individuals
title_short Expression of Vitamin D Receptor Pathway Genes in Subcutaneous Adipose Tissue of Obese Individuals
title_sort expression of vitamin d receptor pathway genes in subcutaneous adipose tissue of obese individuals
topic Pediatric Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090667/
http://dx.doi.org/10.1210/jendso/bvab048.1342
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