Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals

Scope: Vitamin D-3, its biologically most active metabolite 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3), and the vitamin D receptor (VDR) are important for adipose tissue biology. Methods and results: 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 D-3 intervention study, we demonstrated that all four primary VDR target genes can serve as biomarkers for the vitamin D-3 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. Conclusion: 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 D-3.