Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
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- Tomomi Hashidate-Yoshida
- Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
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- Takeshi Harayama
- Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
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- Daisuke Hishikawa
- Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
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- Ryo Morimoto
- Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
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- Fumie Hamano
- Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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- Suzumi M Tokuoka
- Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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- Miki Eto
- Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
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- Miwa Tamura-Nakano
- Communal Laboratory, National Center for Global Health and Medicine, Tokyo, Japan
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- Rieko Yanobu-Takanashi
- Department of Laboratory Animal Medicine, National Center for Global Health and Medicine, Tokyo, Japan
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- Yoshiko Mukumoto
- Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan
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- Hiroshi Kiyonari
- Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan
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- Tadashi Okamura
- Department of Laboratory Animal Medicine, National Center for Global Health and Medicine, Tokyo, Japan
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- Yoshihiro Kita
- Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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- Hideo Shindou
- Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
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- Takao Shimizu
- Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
説明
<jats:p>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.</jats:p>
収録刊行物
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- eLife
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eLife 4 e06328-, 2015-04-21
eLife Sciences Publications, Ltd
