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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/06328 |
| _version_ | 1811199850610425856 |
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| author | Tomomi Hashidate-Yoshida Takeshi Harayama Daisuke Hishikawa Ryo Morimoto Fumie Hamano Suzumi M Tokuoka Miki Eto Miwa Tamura-Nakano Rieko Yanobu-Takanashi Yoshiko Mukumoto Hiroshi Kiyonari Tadashi Okamura Yoshihiro Kita Hideo Shindou Takao Shimizu |
| author_facet | Tomomi Hashidate-Yoshida Takeshi Harayama Daisuke Hishikawa Ryo Morimoto Fumie Hamano Suzumi M Tokuoka Miki Eto Miwa Tamura-Nakano Rieko Yanobu-Takanashi Yoshiko Mukumoto Hiroshi Kiyonari Tadashi Okamura Yoshihiro Kita Hideo Shindou Takao Shimizu |
| author_sort | Tomomi Hashidate-Yoshida |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T01:54:18Z |
| format | Article |
| id | doaj.art-e77477d61e2740d5a54c570fec3d11ef |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:54:18Z |
| publishDate | 2015-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e77477d61e2740d5a54c570fec3d11ef2022-12-22T03:52:51ZengeLife Sciences Publications LtdeLife2050-084X2015-04-01410.7554/eLife.06328Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transportTomomi Hashidate-Yoshida0Takeshi Harayama1Daisuke Hishikawa2Ryo Morimoto3Fumie Hamano4Suzumi M Tokuoka5Miki Eto6Miwa Tamura-Nakano7Rieko Yanobu-Takanashi8Yoshiko Mukumoto9Hiroshi Kiyonari10Tadashi Okamura11Yoshihiro Kita12Hideo Shindou13Takao Shimizu14Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, JapanDepartment of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, JapanDepartment of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, JapanDepartment of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan; Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Life Sciences Core Facility, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan; Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanCommunal Laboratory, National Center for Global Health and Medicine, Tokyo, JapanDepartment of Laboratory Animal Medicine, National Center for Global Health and Medicine, Tokyo, JapanLaboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, JapanLaboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, JapanDepartment of Laboratory Animal Medicine, National Center for Global Health and Medicine, Tokyo, Japan; Section of Animal Models, Department of Infectious Diseases, National Center for Global Health and Medicine, Tokyo, JapanDepartment of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Life Sciences Core Facility, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan; Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Kawaguchi, JapanDepartment of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan; Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanPolyunsaturated 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.https://elifesciences.org/articles/06328arachidonic acidphospholipidlipoproteintriacylglycerol |
| spellingShingle | Tomomi Hashidate-Yoshida Takeshi Harayama Daisuke Hishikawa Ryo Morimoto Fumie Hamano Suzumi M Tokuoka Miki Eto Miwa Tamura-Nakano Rieko Yanobu-Takanashi Yoshiko Mukumoto Hiroshi Kiyonari Tadashi Okamura Yoshihiro Kita Hideo Shindou Takao Shimizu Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport eLife arachidonic acid phospholipid lipoprotein triacylglycerol |
| 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 | arachidonic acid phospholipid lipoprotein triacylglycerol |
| url | https://elifesciences.org/articles/06328 |
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