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

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 perf...

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Autores principales: Martínez-Sena, Teresa, Soluyanova, Polina, Guzmán, Carla, Valdivielso, José Manuel, Castell, José Vicente, Jover, Ramiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175212/
https://www.ncbi.nlm.nih.gov/pubmed/32213983
http://dx.doi.org/10.3390/biom10030493
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author Martínez-Sena, Teresa
Soluyanova, Polina
Guzmán, Carla
Valdivielso, José Manuel
Castell, José Vicente
Jover, Ramiro
author_facet Martínez-Sena, Teresa
Soluyanova, Polina
Guzmán, Carla
Valdivielso, José Manuel
Castell, José Vicente
Jover, Ramiro
author_sort Martínez-Sena, Teresa
collection PubMed
description 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.
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spelling pubmed-71752122020-04-28 The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes Martínez-Sena, Teresa Soluyanova, Polina Guzmán, Carla Valdivielso, José Manuel Castell, José Vicente Jover, Ramiro Biomolecules Article 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. MDPI 2020-03-24 /pmc/articles/PMC7175212/ /pubmed/32213983 http://dx.doi.org/10.3390/biom10030493 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Martínez-Sena, Teresa
Soluyanova, Polina
Guzmán, Carla
Valdivielso, José Manuel
Castell, José Vicente
Jover, Ramiro
The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes
title The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes
title_full The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes
title_fullStr The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes
title_full_unstemmed The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes
title_short The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes
title_sort vitamin d receptor regulates glycerolipid and phospholipid metabolism in human hepatocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175212/
https://www.ncbi.nlm.nih.gov/pubmed/32213983
http://dx.doi.org/10.3390/biom10030493
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