School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Mol Nutr Food Res. 2014 Oct;58(10):2036-45. doi: 10.1002/mnfr.201400291. Epub 2014 Jul 28.
Vitamin D₃, its biologically most active metabolite 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), and the vitamin D receptor (VDR) are important for adipose tissue biology.
We extrapolated genomic VDR association loci in adipocytes from 55 conserved genome-wide VDR-binding sites in nonfat tissues. Taking the genes DUSP10, TRAK1, NRIP1, and THBD as examples, we confirmed the predicted VDR binding sites upstream of their transcription start sites and showed rapid mRNA up-regulation of all four genes in SGBS human pre-adipocytes. Using adipose tissue biopsy samples from 47 participants of a 5-month vitamin D₃ intervention study, we demonstrated that all four primary VDR target genes can serve as biomarkers for the vitamin D₃ responsiveness of human individuals. Changes in DUSP10 gene expression appear to be the most comprehensive marker, while THBD mRNA changes characterized a rather different group of study participants.
We present a new approach to predict vitamin D target genes based on conserved genomic VDR-binding sites. Using human adipocytes as examples, we show that such ubiquitous VDR target genes can be used as markers for the individual's response to a supplementation with vitamin D₃.
维生素 D₃、其生物活性最强的代谢产物 1α,25-二羟维生素 D₃（1,25(OH)₂D₃）和维生素 D 受体（VDR）对于脂肪组织生物学很重要。
我们从非脂肪组织中 55 个保守的全基因组 VDR 结合位点推断出脂肪细胞中的基因组 VDR 关联基因座。以 DUSP10、TRAK1、NRIP1 和 THBD 基因为例，我们在它们的转录起始位点上游证实了预测的 VDR 结合位点，并在 SGBS 人类前脂肪细胞中显示了所有四个基因的快速 mRNA 上调。使用来自 47 名参加为期 5 个月的维生素 D₃ 干预研究的参与者的脂肪组织活检样本，我们证明了所有四个主要的 VDR 靶基因都可以作为人类个体对维生素 D₃反应性的生物标志物。DUSP10 基因表达的变化似乎是最全面的标志物，而 THBD mRNA 的变化则描述了一组截然不同的研究参与者。
我们提出了一种基于保守的全基因组 VDR 结合位点预测维生素 D 靶基因的新方法。我们以人类脂肪细胞为例，表明这种普遍存在的 VDR 靶基因可作为个体对维生素 D₃补充反应的标志物。
