The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes
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The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes

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The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes

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dc.contributor.author Martínez-Sena, Teresa
dc.contributor.author Soluyanova, Polina
dc.contributor.author Guzmán, Carla
dc.contributor.author Valdivielso, Jose Manuel
dc.contributor.author Castell Ripoll, José Vicente
dc.contributor.author Jover Atienza, Ramiro
dc.date.accessioned 2020-06-18T10:28:39Z
dc.date.available 2020-06-18T10:28:39Z
dc.date.issued 2020
dc.identifier.uri https://hdl.handle.net/10550/75128
dc.description.abstract 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 (4-6 h) upon VDR activation by 10 nM VitD or 100 µM 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.
dc.language.iso eng
dc.relation.ispartof Biomolecules, 2020, vol. 10, num. 3, p. 493
dc.rights.uri info:eu-repo/semantics/openAccess
dc.source Martínez-Sena, Teresa Soluyanova, Polina Guzmán, Carla Valdivielso, Jose Manuel Castell Ripoll, José Vicente Jover Atienza, Ramiro 2020 The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes Biomolecules 10 3 493
dc.subject Vitamines
dc.subject Cèl·lules
dc.subject Biomolècules
dc.title The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes
dc.type info:eu-repo/semantics/article
dc.date.updated 2020-06-18T10:28:39Z
dc.identifier.doi https://doi.org/10.3390/biom10030493
dc.identifier.idgrec 139722

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