{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:14:57Z","timestamp":1791944097542,"version":"4.3.4"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/01089"],"award-info":[{"award-number":["PI17\/01089"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/00610"],"award-info":[{"award-number":["PI18\/00610"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The vitamin D receptor (VDR) must be relevant to liver lipid metabolism because VDR deficient mice are protected from hepatosteatosis. Therefore, our objective was to define the role of VDR on the overall lipid metabolism in human hepatocytes. We developed an adenoviral vector for human VDR and performed transcriptomic and metabolomic analyses of cultured human hepatocytes upon VDR activation by vitamin D (VitD). Twenty percent of the VDR responsive genes were related to lipid metabolism, including MOGAT1, LPGAT1, AGPAT2, and DGAT1 (glycerolipid metabolism); CDS1, PCTP, and MAT1A (phospholipid metabolism); and FATP2, SLC6A12, and AQP3 (uptake of fatty acids, betaine, and glycerol, respectively). They were rapidly induced (4\u20136 h) upon VDR activation by 10 nM VitD or 100 \u00b5M lithocholic acid (LCA). Most of these genes were also upregulated by VDR\/VitD in mouse livers in vivo. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) metabolomics demonstrated intracellular accumulation of triglycerides, with concomitant decreases in diglycerides and phosphatidates, at 8 and 24 h upon VDR activation. Significant alterations in phosphatidylcholines, increases in lyso-phosphatidylcholines and decreases in phosphatidylethanolamines and phosphatidylethanolamine plasmalogens were also observed. In conclusion, active VitD\/VDR signaling in hepatocytes triggers an unanticipated coordinated gene response leading to triglyceride synthesis and to important perturbations in glycerolipids and phospholipids.<\/jats:p>","DOI":"10.3390\/biom10030493","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T13:04:04Z","timestamp":1585055044000},"page":"493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes"],"prefix":"10.3390","volume":"10","author":[{"given":"Teresa","family":"Mart\u00ednez-Sena","sequence":"first","affiliation":[{"name":"Experimental Hepatology Unit, IIS Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Soluyanova","sequence":"additional","affiliation":[{"name":"Experimental Hepatology Unit, IIS Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Experimental Hepatology Unit, IIS Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1343-0184","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"Valdivielso","sequence":"additional","affiliation":[{"name":"Vascular and Renal Translational Research Group, Experimental Medicine Department, IRBLleida, 25196 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1179-6430","authenticated-orcid":false,"given":"Jos\u00e9 Vicente","family":"Castell","sequence":"additional","affiliation":[{"name":"Experimental Hepatology Unit, IIS Hospital La Fe, 46026 Valencia, Spain"},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4914-5804","authenticated-orcid":false,"given":"Ramiro","family":"Jover","sequence":"additional","affiliation":[{"name":"Experimental Hepatology Unit, IIS Hospital La Fe, 46026 Valencia, Spain"},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.cell.2006.06.049","article-title":"Anatomical Profiling of Nuclear Receptor Expression Reveals a Hierarchical Transcriptional Network","volume":"126","author":"Bookout","year":"2006","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1210\/er.2008-0004","article-title":"Vitamin D and human health: Lessons from vitamin D receptor null mice","volume":"29","author":"Bouillon","year":"2008","journal-title":"Endocr. 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