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Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion
The role of specific phospholipids (PLs) in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of tr...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400582/ https://www.ncbi.nlm.nih.gov/pubmed/25806685 http://dx.doi.org/10.7554/eLife.06557 |
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author | Rong, Xin Wang, Bo Dunham, Merlow M Hedde, Per Niklas Wong, Jinny S Gratton, Enrico Young, Stephen G Ford, David A Tontonoz, Peter |
author_facet | Rong, Xin Wang, Bo Dunham, Merlow M Hedde, Per Niklas Wong, Jinny S Gratton, Enrico Young, Stephen G Ford, David A Tontonoz, Peter |
author_sort | Rong, Xin |
collection | PubMed |
description | The role of specific phospholipids (PLs) in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of triglyceride (TG) secretion due to its unique ability to catalyze the incorporation of arachidonate into membranes. Mice lacking Lpcat3 in the intestine fail to thrive during weaning and exhibit enterocyte lipid accumulation and reduced plasma TGs. Mice lacking Lpcat3 in the liver show reduced plasma TGs, hepatosteatosis, and secrete lipid-poor very low-density lipoprotein (VLDL) lacking arachidonoyl PLs. Mechanistic studies indicate that Lpcat3 activity impacts membrane lipid mobility in living cells, suggesting a biophysical basis for the requirement of arachidonoyl PLs in lipidating lipoprotein particles. These data identify Lpcat3 as a key factor in lipoprotein production and illustrate how manipulation of membrane composition can be used as a regulatory mechanism to control metabolic pathways. DOI: http://dx.doi.org/10.7554/eLife.06557.001 |
format | Online Article Text |
id | pubmed-4400582 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-44005822015-04-20 Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion Rong, Xin Wang, Bo Dunham, Merlow M Hedde, Per Niklas Wong, Jinny S Gratton, Enrico Young, Stephen G Ford, David A Tontonoz, Peter eLife Cell Biology The role of specific phospholipids (PLs) in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of triglyceride (TG) secretion due to its unique ability to catalyze the incorporation of arachidonate into membranes. Mice lacking Lpcat3 in the intestine fail to thrive during weaning and exhibit enterocyte lipid accumulation and reduced plasma TGs. Mice lacking Lpcat3 in the liver show reduced plasma TGs, hepatosteatosis, and secrete lipid-poor very low-density lipoprotein (VLDL) lacking arachidonoyl PLs. Mechanistic studies indicate that Lpcat3 activity impacts membrane lipid mobility in living cells, suggesting a biophysical basis for the requirement of arachidonoyl PLs in lipidating lipoprotein particles. These data identify Lpcat3 as a key factor in lipoprotein production and illustrate how manipulation of membrane composition can be used as a regulatory mechanism to control metabolic pathways. DOI: http://dx.doi.org/10.7554/eLife.06557.001 eLife Sciences Publications, Ltd 2015-03-25 /pmc/articles/PMC4400582/ /pubmed/25806685 http://dx.doi.org/10.7554/eLife.06557 Text en © 2015, Rong et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Rong, Xin Wang, Bo Dunham, Merlow M Hedde, Per Niklas Wong, Jinny S Gratton, Enrico Young, Stephen G Ford, David A Tontonoz, Peter Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion |
title | Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion |
title_full | Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion |
title_fullStr | Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion |
title_full_unstemmed | Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion |
title_short | Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion |
title_sort | lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400582/ https://www.ncbi.nlm.nih.gov/pubmed/25806685 http://dx.doi.org/10.7554/eLife.06557 |
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