4.7 Article

Vitamin D Receptor Gene Expression in Adipose Tissue of Obese Individuals is Regulated by miRNA and Correlates with the Pro-Inflammatory Cytokine Level

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出版社

MDPI
DOI: 10.3390/ijms20215272

关键词

adipose tissue; obesity; vitamin D receptor (VDR); micro RNA (miRNA); pro-inflammatory cytokines

资金

  1. National Science Centre Poland [2012/05/B/NZ5/01536]
  2. Polish Ministry of Science and Higher Education [NN402 467939]
  3. Mossakowski Medical Research Centre, PAS

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Background: Given the role that vitamin D (VD) plays in the regulation of the inflammatory activity of adipocytes, we aimed to assess whether obesity changes the expression of VD-related genes in adipose tissue and, if so, to investigate whether this phenomenon depends on microRNA interference and how it may influence the local inflammatory milieu. Methods: The expression of genes encoding VD 1 alpha-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and receptor (VDR), selected interleukins and microRNAs was evaluated by real-time PCR in visceral (VAT) and in subcutaneous (SAT) adipose tissues of 55 obese (BMI > 40 kg/m(2)) and 31 normal-weight (BMI 20-24.9 kg/m(2)) individuals. Results: VDR mRNA levels were higher, while CYP27B1 levels were lower in adipose tissues of obese patients than in those of normal-weight controls (VAT: P = 0.04, SAT: P < 0.0001 and VAT: P = 0.004, SAT: P = 0.016, respectively). The expression of VDR in VAT of obese subjects correlated negatively with levels of miR-125a-5p (P = 0.0006, r(s) = -0.525), miR-125b-5p (P = 0.001, r(s) = -0.495), and miR-214-3p (P = 0.009, r(s) = -0.379). Additionally, VDR mRNA concentrations in visceral adipose tissues of obese subjects correlated positively with mRNA levels of interleukins: 1 beta, 6 and 8. Conclusions: We observed obesity-associated up-regulation of VDR and down-regulation of CYP27B mRNA levels in adipose tissue. VDR expression correlates with the expression of pro-inflammatory cytokines and may be regulated by miRNAs.

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