Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals
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 sit...
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| Veröffentlicht in: | Molecular nutrition & food research 2014-10, Vol.58 (10), p.2036-2045 |
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| creator | Ryynänen, Jussi Neme, Antonio Tuomainen, Tomi‐Pekka Virtanen, Jyrki K Voutilainen, Sari Nurmi, Tarja Mello, Vanessa D. F Uusitupa, Matti Carlberg, Carsten |
| description | 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. |
| doi_str_mv | 10.1002/mnfr.201400291 |
| format | Article |
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F ; Uusitupa, Matti ; Carlberg, Carsten</creator><creatorcontrib>Ryynänen, Jussi ; Neme, Antonio ; Tuomainen, Tomi‐Pekka ; Virtanen, Jyrki K ; Voutilainen, Sari ; Nurmi, Tarja ; Mello, Vanessa D. F ; Uusitupa, Matti ; Carlberg, Carsten</creatorcontrib><description>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.</description><identifier>ISSN: 1613-4125</identifier><identifier>EISSN: 1613-4133</identifier><identifier>DOI: 10.1002/mnfr.201400291</identifier><identifier>PMID: 24975273</identifier><language>eng</language><publisher>Weinheim: Wiley-VCH</publisher><subject>Adaptor Proteins, Signal Transducing - agonists ; Adaptor Proteins, Signal Transducing - chemistry ; Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Adaptor Proteins, Vesicular Transport - agonists ; Adaptor Proteins, Vesicular Transport - chemistry ; Adaptor Proteins, Vesicular Transport - genetics ; Adaptor Proteins, Vesicular Transport - metabolism ; adipocytes ; Adipose tissue ; Adipose Tissue - metabolism ; Adipose Tissue - pathology ; Aged ; binding sites ; Biological and medical sciences ; biomarkers ; Biomarkers - metabolism ; biopsy ; Calcitriol - metabolism ; Cell Line ; Cells, Cultured ; cholecalciferol ; Cholecalciferol - administration & dosage ; Cholecalciferol - deficiency ; Cholecalciferol - metabolism ; Cholecalciferol - therapeutic use ; Chromatin immunoprecipitation ; Conserved Sequence ; Dietary Supplements ; Dual-Specificity Phosphatases - chemistry ; Dual-Specificity Phosphatases - genetics ; Dual-Specificity Phosphatases - metabolism ; Feeding. Feeding behavior ; Finland ; Fundamental and applied biological sciences. Psychology ; gene expression ; gene expression regulation ; genes ; Humans ; loci ; Male ; messenger RNA ; metabolites ; Mitogen-Activated Protein Kinase Phosphatases - chemistry ; Mitogen-Activated Protein Kinase Phosphatases - genetics ; Mitogen-Activated Protein Kinase Phosphatases - metabolism ; Nuclear Proteins - agonists ; Nuclear Proteins - chemistry ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Receptors, Calcitriol - agonists ; Receptors, Calcitriol - genetics ; Receptors, Calcitriol - metabolism ; RNA, Messenger - metabolism ; Seasons ; Thrombomodulin - agonists ; Thrombomodulin - chemistry ; Thrombomodulin - genetics ; Thrombomodulin - metabolism ; Up-Regulation ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Vitamin D ; Vitamin D Deficiency - diet therapy ; Vitamin D Deficiency - metabolism ; Vitamin D Deficiency - pathology ; Vitamin D receptor ; Vitamin D Response Element ; Vitamin D target genes</subject><ispartof>Molecular nutrition & food research, 2014-10, Vol.58 (10), p.2036-2045</ispartof><rights>2014 WILEY‐VCH Verlag GmbH & Co. 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F</creatorcontrib><creatorcontrib>Uusitupa, Matti</creatorcontrib><creatorcontrib>Carlberg, Carsten</creatorcontrib><title>Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals</title><title>Molecular nutrition & food research</title><addtitle>Mol. Nutr. Food Res</addtitle><description>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.</description><subject>Adaptor Proteins, Signal Transducing - agonists</subject><subject>Adaptor Proteins, Signal Transducing - chemistry</subject><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Adaptor Proteins, Vesicular Transport - agonists</subject><subject>Adaptor Proteins, Vesicular Transport - chemistry</subject><subject>Adaptor Proteins, Vesicular Transport - genetics</subject><subject>Adaptor Proteins, Vesicular Transport - metabolism</subject><subject>adipocytes</subject><subject>Adipose tissue</subject><subject>Adipose Tissue - metabolism</subject><subject>Adipose Tissue - pathology</subject><subject>Aged</subject><subject>binding sites</subject><subject>Biological and medical sciences</subject><subject>biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>biopsy</subject><subject>Calcitriol - metabolism</subject><subject>Cell Line</subject><subject>Cells, Cultured</subject><subject>cholecalciferol</subject><subject>Cholecalciferol - administration & dosage</subject><subject>Cholecalciferol - deficiency</subject><subject>Cholecalciferol - metabolism</subject><subject>Cholecalciferol - therapeutic use</subject><subject>Chromatin immunoprecipitation</subject><subject>Conserved Sequence</subject><subject>Dietary Supplements</subject><subject>Dual-Specificity Phosphatases - chemistry</subject><subject>Dual-Specificity Phosphatases - genetics</subject><subject>Dual-Specificity Phosphatases - metabolism</subject><subject>Feeding. Feeding behavior</subject><subject>Finland</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>gene expression</subject><subject>gene expression regulation</subject><subject>genes</subject><subject>Humans</subject><subject>loci</subject><subject>Male</subject><subject>messenger RNA</subject><subject>metabolites</subject><subject>Mitogen-Activated Protein Kinase Phosphatases - chemistry</subject><subject>Mitogen-Activated Protein Kinase Phosphatases - genetics</subject><subject>Mitogen-Activated Protein Kinase Phosphatases - metabolism</subject><subject>Nuclear Proteins - agonists</subject><subject>Nuclear Proteins - chemistry</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Receptors, Calcitriol - agonists</subject><subject>Receptors, Calcitriol - genetics</subject><subject>Receptors, Calcitriol - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Seasons</subject><subject>Thrombomodulin - agonists</subject><subject>Thrombomodulin - chemistry</subject><subject>Thrombomodulin - genetics</subject><subject>Thrombomodulin - metabolism</subject><subject>Up-Regulation</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>Vitamin D</subject><subject>Vitamin D Deficiency - diet therapy</subject><subject>Vitamin D Deficiency - metabolism</subject><subject>Vitamin D Deficiency - pathology</subject><subject>Vitamin D receptor</subject><subject>Vitamin D Response Element</subject><subject>Vitamin D target genes</subject><issn>1613-4125</issn><issn>1613-4133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhSMEoqVw5Qi5IHHJYo_txDmiLd0ilUWCdjla3mS8a0ji1E5K--9xlGXh1tOzpe89z_glyWtKFpQQ-NB2xi-AUB4vJX2SnNKcsoxTxp4ezyBOkhch_CSEUeDseXICvCwEFOw0uV3udbfDkNouvbODbqOep4P2OxzSHXaY4n3vMQTruonRte1dwHSwIYyYtq6zg_PpsMf_7JHvXRcpZ9L92OrJWds7W4-6CS-TZyYKvjroWXJz8el6eZldfV19Xn68yqqccMigpjVwXnAqOQEjeAWlqYramC1gQUVZs1rzgm4JcGAodfwOYbaCQAU5lQU7S97Pub13tyOGQbU2VNg0ukM3BkXznLCSyOh-FBUyJ6Vk5ZS6mNHKuxA8GtV722r_oChRUyNqakQdG4mGN4fscdtifcT_VhCBdwdAh0o3xuuusuEfJ6WIWSJyfOZ-2wYfHnlWfVlffANg027ZbLNhwPujTftfKi9YIdSP9Uqt1pvNZnl9qaYF38680U7pnY-j3HyPuYIQIgmFkv0Bl0G75w</recordid><startdate>201410</startdate><enddate>201410</enddate><creator>Ryynänen, Jussi</creator><creator>Neme, Antonio</creator><creator>Tuomainen, Tomi‐Pekka</creator><creator>Virtanen, Jyrki K</creator><creator>Voutilainen, Sari</creator><creator>Nurmi, Tarja</creator><creator>Mello, Vanessa D. F</creator><creator>Uusitupa, Matti</creator><creator>Carlberg, Carsten</creator><general>Wiley-VCH</general><general>Blackwell Publishing Ltd</general><general>Wiley</general><scope>FBQ</scope><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>201410</creationdate><title>Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals</title><author>Ryynänen, Jussi ; Neme, Antonio ; Tuomainen, Tomi‐Pekka ; Virtanen, Jyrki K ; Voutilainen, Sari ; Nurmi, Tarja ; Mello, Vanessa D. 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Psychology</topic><topic>gene expression</topic><topic>gene expression regulation</topic><topic>genes</topic><topic>Humans</topic><topic>loci</topic><topic>Male</topic><topic>messenger RNA</topic><topic>metabolites</topic><topic>Mitogen-Activated Protein Kinase Phosphatases - chemistry</topic><topic>Mitogen-Activated Protein Kinase Phosphatases - genetics</topic><topic>Mitogen-Activated Protein Kinase Phosphatases - metabolism</topic><topic>Nuclear Proteins - agonists</topic><topic>Nuclear Proteins - chemistry</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Receptors, Calcitriol - agonists</topic><topic>Receptors, Calcitriol - genetics</topic><topic>Receptors, Calcitriol - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Seasons</topic><topic>Thrombomodulin - agonists</topic><topic>Thrombomodulin - chemistry</topic><topic>Thrombomodulin - genetics</topic><topic>Thrombomodulin - metabolism</topic><topic>Up-Regulation</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Vitamin D</topic><topic>Vitamin D Deficiency - diet therapy</topic><topic>Vitamin D Deficiency - metabolism</topic><topic>Vitamin D Deficiency - pathology</topic><topic>Vitamin D receptor</topic><topic>Vitamin D Response Element</topic><topic>Vitamin D target genes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ryynänen, Jussi</creatorcontrib><creatorcontrib>Neme, Antonio</creatorcontrib><creatorcontrib>Tuomainen, Tomi‐Pekka</creatorcontrib><creatorcontrib>Virtanen, Jyrki K</creatorcontrib><creatorcontrib>Voutilainen, Sari</creatorcontrib><creatorcontrib>Nurmi, Tarja</creatorcontrib><creatorcontrib>Mello, Vanessa D. 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F</au><au>Uusitupa, Matti</au><au>Carlberg, Carsten</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals</atitle><jtitle>Molecular nutrition & food research</jtitle><addtitle>Mol. Nutr. Food Res</addtitle><date>2014-10</date><risdate>2014</risdate><volume>58</volume><issue>10</issue><spage>2036</spage><epage>2045</epage><pages>2036-2045</pages><issn>1613-4125</issn><eissn>1613-4133</eissn><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. 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| subjects | Adaptor Proteins, Signal Transducing - agonists Adaptor Proteins, Signal Transducing - chemistry Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Adaptor Proteins, Vesicular Transport - agonists Adaptor Proteins, Vesicular Transport - chemistry Adaptor Proteins, Vesicular Transport - genetics Adaptor Proteins, Vesicular Transport - metabolism adipocytes Adipose tissue Adipose Tissue - metabolism Adipose Tissue - pathology Aged binding sites Biological and medical sciences biomarkers Biomarkers - metabolism biopsy Calcitriol - metabolism Cell Line Cells, Cultured cholecalciferol Cholecalciferol - administration & dosage Cholecalciferol - deficiency Cholecalciferol - metabolism Cholecalciferol - therapeutic use Chromatin immunoprecipitation Conserved Sequence Dietary Supplements Dual-Specificity Phosphatases - chemistry Dual-Specificity Phosphatases - genetics Dual-Specificity Phosphatases - metabolism Feeding. Feeding behavior Finland Fundamental and applied biological sciences. Psychology gene expression gene expression regulation genes Humans loci Male messenger RNA metabolites Mitogen-Activated Protein Kinase Phosphatases - chemistry Mitogen-Activated Protein Kinase Phosphatases - genetics Mitogen-Activated Protein Kinase Phosphatases - metabolism Nuclear Proteins - agonists Nuclear Proteins - chemistry Nuclear Proteins - genetics Nuclear Proteins - metabolism Receptors, Calcitriol - agonists Receptors, Calcitriol - genetics Receptors, Calcitriol - metabolism RNA, Messenger - metabolism Seasons Thrombomodulin - agonists Thrombomodulin - chemistry Thrombomodulin - genetics Thrombomodulin - metabolism Up-Regulation Vertebrates: anatomy and physiology, studies on body, several organs or systems Vitamin D Vitamin D Deficiency - diet therapy Vitamin D Deficiency - metabolism Vitamin D Deficiency - pathology Vitamin D receptor Vitamin D Response Element Vitamin D target genes |
| title | Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals |
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