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Lysophosphatidic Acid Activates Peroxisome Proliferator Activated Receptor-γ in CHO Cells That Over-Express Glycerol 3-Phosphate Acyltransferase-1

Lysophosphatidic acid (LPA) is an agonist for peroxisome proliferator activated receptor-γ (PPARγ). Although glycerol-3-phosphate acyltransferase-1 (GPAT1) esterifies glycerol-3-phosphate to form LPA, an intermediate in the de novo synthesis of glycerolipids, it has been assumed that LPA synthesized...

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Autores principales: Stapleton, Cliona M., Mashek, Douglas G., Wang, Shuli, Nagle, Cynthia A., Cline, Gary W., Thuillier, Philippe, Leesnitzer, Lisa M., Li, Lei O., Stimmel, Julie B., Shulman, Gerald I., Coleman, Rosalind A.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080373/
https://www.ncbi.nlm.nih.gov/pubmed/21533082
http://dx.doi.org/10.1371/journal.pone.0018932
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author Stapleton, Cliona M.
Mashek, Douglas G.
Wang, Shuli
Nagle, Cynthia A.
Cline, Gary W.
Thuillier, Philippe
Leesnitzer, Lisa M.
Li, Lei O.
Stimmel, Julie B.
Shulman, Gerald I.
Coleman, Rosalind A.
author_facet Stapleton, Cliona M.
Mashek, Douglas G.
Wang, Shuli
Nagle, Cynthia A.
Cline, Gary W.
Thuillier, Philippe
Leesnitzer, Lisa M.
Li, Lei O.
Stimmel, Julie B.
Shulman, Gerald I.
Coleman, Rosalind A.
author_sort Stapleton, Cliona M.
collection PubMed
description Lysophosphatidic acid (LPA) is an agonist for peroxisome proliferator activated receptor-γ (PPARγ). Although glycerol-3-phosphate acyltransferase-1 (GPAT1) esterifies glycerol-3-phosphate to form LPA, an intermediate in the de novo synthesis of glycerolipids, it has been assumed that LPA synthesized by this route does not have a signaling role. The availability of Chinese Hamster Ovary (CHO) cells that stably overexpress GPAT1, allowed us to analyze PPARγ activation in the presence of LPA produced as an intracellular intermediate. LPA levels in CHO-GPAT1 cells were 6-fold higher than in wild-type CHO cells, and the mRNA abundance of CD36, a PPARγ target, was 2-fold higher. Transactivation assays showed that PPARγ activity was higher in the cells that overexpressed GPAT1. PPARγ activity was enhanced further in CHO-GPAT1 cells treated with the PPARγ ligand troglitazone. Extracellular LPA, phosphatidic acid (PA) or a membrane-permeable diacylglycerol had no effect, showing that PPARγ had been activated by LPA generated intracellularly. Transient transfection of a vector expressing 1-acylglycerol-3-phosphate acyltransferase-2, which converts endogenous LPA to PA, markedly reduced PPARγ activity, as did over-expressing diacylglycerol kinase, which converts DAG to PA, indicating that PA could be a potent inhibitor of PPARγ. These data suggest that LPA synthesized via the glycerol-3-phosphate pathway can activate PPARγ and that intermediates of de novo glycerolipid synthesis regulate gene expression.
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spelling pubmed-30803732011-04-29 Lysophosphatidic Acid Activates Peroxisome Proliferator Activated Receptor-γ in CHO Cells That Over-Express Glycerol 3-Phosphate Acyltransferase-1 Stapleton, Cliona M. Mashek, Douglas G. Wang, Shuli Nagle, Cynthia A. Cline, Gary W. Thuillier, Philippe Leesnitzer, Lisa M. Li, Lei O. Stimmel, Julie B. Shulman, Gerald I. Coleman, Rosalind A. PLoS One Research Article Lysophosphatidic acid (LPA) is an agonist for peroxisome proliferator activated receptor-γ (PPARγ). Although glycerol-3-phosphate acyltransferase-1 (GPAT1) esterifies glycerol-3-phosphate to form LPA, an intermediate in the de novo synthesis of glycerolipids, it has been assumed that LPA synthesized by this route does not have a signaling role. The availability of Chinese Hamster Ovary (CHO) cells that stably overexpress GPAT1, allowed us to analyze PPARγ activation in the presence of LPA produced as an intracellular intermediate. LPA levels in CHO-GPAT1 cells were 6-fold higher than in wild-type CHO cells, and the mRNA abundance of CD36, a PPARγ target, was 2-fold higher. Transactivation assays showed that PPARγ activity was higher in the cells that overexpressed GPAT1. PPARγ activity was enhanced further in CHO-GPAT1 cells treated with the PPARγ ligand troglitazone. Extracellular LPA, phosphatidic acid (PA) or a membrane-permeable diacylglycerol had no effect, showing that PPARγ had been activated by LPA generated intracellularly. Transient transfection of a vector expressing 1-acylglycerol-3-phosphate acyltransferase-2, which converts endogenous LPA to PA, markedly reduced PPARγ activity, as did over-expressing diacylglycerol kinase, which converts DAG to PA, indicating that PA could be a potent inhibitor of PPARγ. These data suggest that LPA synthesized via the glycerol-3-phosphate pathway can activate PPARγ and that intermediates of de novo glycerolipid synthesis regulate gene expression. Public Library of Science 2011-04-20 /pmc/articles/PMC3080373/ /pubmed/21533082 http://dx.doi.org/10.1371/journal.pone.0018932 Text en Stapleton et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Stapleton, Cliona M.
Mashek, Douglas G.
Wang, Shuli
Nagle, Cynthia A.
Cline, Gary W.
Thuillier, Philippe
Leesnitzer, Lisa M.
Li, Lei O.
Stimmel, Julie B.
Shulman, Gerald I.
Coleman, Rosalind A.
Lysophosphatidic Acid Activates Peroxisome Proliferator Activated Receptor-γ in CHO Cells That Over-Express Glycerol 3-Phosphate Acyltransferase-1
title Lysophosphatidic Acid Activates Peroxisome Proliferator Activated Receptor-γ in CHO Cells That Over-Express Glycerol 3-Phosphate Acyltransferase-1
title_full Lysophosphatidic Acid Activates Peroxisome Proliferator Activated Receptor-γ in CHO Cells That Over-Express Glycerol 3-Phosphate Acyltransferase-1
title_fullStr Lysophosphatidic Acid Activates Peroxisome Proliferator Activated Receptor-γ in CHO Cells That Over-Express Glycerol 3-Phosphate Acyltransferase-1
title_full_unstemmed Lysophosphatidic Acid Activates Peroxisome Proliferator Activated Receptor-γ in CHO Cells That Over-Express Glycerol 3-Phosphate Acyltransferase-1
title_short Lysophosphatidic Acid Activates Peroxisome Proliferator Activated Receptor-γ in CHO Cells That Over-Express Glycerol 3-Phosphate Acyltransferase-1
title_sort lysophosphatidic acid activates peroxisome proliferator activated receptor-γ in cho cells that over-express glycerol 3-phosphate acyltransferase-1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080373/
https://www.ncbi.nlm.nih.gov/pubmed/21533082
http://dx.doi.org/10.1371/journal.pone.0018932
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