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Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport

Polyunsaturated fatty acids (PUFAs) in phospholipids affect the physical properties of membranes, but it is unclear which biological processes are influenced by their regulation. For example, the functions of membrane arachidonate that are independent of a precursor role for eicosanoid synthesis rem...

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Autores principales: Hashidate-Yoshida, Tomomi, Harayama, Takeshi, Hishikawa, Daisuke, Morimoto, Ryo, Hamano, Fumie, Tokuoka, Suzumi M, Eto, Miki, Tamura-Nakano, Miwa, Yanobu-Takanashi, Rieko, Mukumoto, Yoshiko, Kiyonari, Hiroshi, Okamura, Tadashi, Kita, Yoshihiro, Shindou, Hideo, Shimizu, Takao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436788/
https://www.ncbi.nlm.nih.gov/pubmed/25898003
http://dx.doi.org/10.7554/eLife.06328
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author Hashidate-Yoshida, Tomomi
Harayama, Takeshi
Hishikawa, Daisuke
Morimoto, Ryo
Hamano, Fumie
Tokuoka, Suzumi M
Eto, Miki
Tamura-Nakano, Miwa
Yanobu-Takanashi, Rieko
Mukumoto, Yoshiko
Kiyonari, Hiroshi
Okamura, Tadashi
Kita, Yoshihiro
Shindou, Hideo
Shimizu, Takao
author_facet Hashidate-Yoshida, Tomomi
Harayama, Takeshi
Hishikawa, Daisuke
Morimoto, Ryo
Hamano, Fumie
Tokuoka, Suzumi M
Eto, Miki
Tamura-Nakano, Miwa
Yanobu-Takanashi, Rieko
Mukumoto, Yoshiko
Kiyonari, Hiroshi
Okamura, Tadashi
Kita, Yoshihiro
Shindou, Hideo
Shimizu, Takao
author_sort Hashidate-Yoshida, Tomomi
collection PubMed
description Polyunsaturated fatty acids (PUFAs) in phospholipids affect the physical properties of membranes, but it is unclear which biological processes are influenced by their regulation. For example, the functions of membrane arachidonate that are independent of a precursor role for eicosanoid synthesis remain largely unknown. Here, we show that the lack of lysophosphatidylcholine acyltransferase 3 (LPCAT3) leads to drastic reductions in membrane arachidonate levels, and that LPCAT3-deficient mice are neonatally lethal due to an extensive triacylglycerol (TG) accumulation and dysfunction in enterocytes. We found that high levels of PUFAs in membranes enable TGs to locally cluster in high density, and that this clustering promotes efficient TG transfer. We propose a model of local arachidonate enrichment by LPCAT3 to generate a distinct pool of TG in membranes, which is required for normal directionality of TG transfer and lipoprotein assembly in the liver and enterocytes. DOI: http://dx.doi.org/10.7554/eLife.06328.001
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spelling pubmed-44367882015-05-20 Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport Hashidate-Yoshida, Tomomi Harayama, Takeshi Hishikawa, Daisuke Morimoto, Ryo Hamano, Fumie Tokuoka, Suzumi M Eto, Miki Tamura-Nakano, Miwa Yanobu-Takanashi, Rieko Mukumoto, Yoshiko Kiyonari, Hiroshi Okamura, Tadashi Kita, Yoshihiro Shindou, Hideo Shimizu, Takao eLife Biochemistry Polyunsaturated fatty acids (PUFAs) in phospholipids affect the physical properties of membranes, but it is unclear which biological processes are influenced by their regulation. For example, the functions of membrane arachidonate that are independent of a precursor role for eicosanoid synthesis remain largely unknown. Here, we show that the lack of lysophosphatidylcholine acyltransferase 3 (LPCAT3) leads to drastic reductions in membrane arachidonate levels, and that LPCAT3-deficient mice are neonatally lethal due to an extensive triacylglycerol (TG) accumulation and dysfunction in enterocytes. We found that high levels of PUFAs in membranes enable TGs to locally cluster in high density, and that this clustering promotes efficient TG transfer. We propose a model of local arachidonate enrichment by LPCAT3 to generate a distinct pool of TG in membranes, which is required for normal directionality of TG transfer and lipoprotein assembly in the liver and enterocytes. DOI: http://dx.doi.org/10.7554/eLife.06328.001 eLife Sciences Publications, Ltd 2015-04-21 /pmc/articles/PMC4436788/ /pubmed/25898003 http://dx.doi.org/10.7554/eLife.06328 Text en © 2015, Hashidate-Yoshida 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 Biochemistry
Hashidate-Yoshida, Tomomi
Harayama, Takeshi
Hishikawa, Daisuke
Morimoto, Ryo
Hamano, Fumie
Tokuoka, Suzumi M
Eto, Miki
Tamura-Nakano, Miwa
Yanobu-Takanashi, Rieko
Mukumoto, Yoshiko
Kiyonari, Hiroshi
Okamura, Tadashi
Kita, Yoshihiro
Shindou, Hideo
Shimizu, Takao
Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
title Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
title_full Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
title_fullStr Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
title_full_unstemmed Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
title_short Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
title_sort fatty acid remodeling by lpcat3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436788/
https://www.ncbi.nlm.nih.gov/pubmed/25898003
http://dx.doi.org/10.7554/eLife.06328
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