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

Jussi Ryynänen, Antonio Neme, Tomi-Pekka Tuomainen, Jyrki K Virtanen, Sari Voutilainen, Tarja Nurmi, Vanessa D F de Mello, Matti Uusitupa, Carsten Carlberg

Journal: Molecular nutrition & food research 2015;58(10):2036-45

PMID: 24975273

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Abstract

SCOPE

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.

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 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.

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 D₃.

Address: School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.

DOI: 10.1002/mnfr.201400291

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MeSH Terms: Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Adipose Tissue, Aged, Biomarkers, Calcitriol, Cell Line, Cells, Cultured, Cholecalciferol, Conserved Sequence, Dietary Supplements, Dual-Specificity Phosphatases, Finland, Humans, Male, Mitogen-Activated Protein Kinase Phosphatases, Nuclear Proteins, Nuclear Receptor Interacting Protein 1, RNA, Messenger, Receptors, Calcitriol, Seasons, Thrombomodulin, Up-Regulation, Vitamin D Deficiency, Vitamin D Response Element