1. Biochemistry and Chemical Biology

Fatty acyl-chain remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport

  1. Tomomi Hashidate-Yoshida
  2. Takeshi Harayama
  3. Daisuke Hishikawa
  4. Ryo Morimoto
  5. Fumie Hamano
  6. Suzumi M Tokuoka
  7. Miki Eto
  8. Miwa Tamura-Nakano
  9. Rieko Yanobu-Takanashi
  10. Yoshiko Mukumoto
  11. Hiroshi Kiyonari
  12. Tadashi Okamura
  13. Yoshihiro Kita
  14. Hideo Shindou
  15. Takao Shimizu  Is a corresponding author
  1. National Center for Global Health and Medicine, Japan
  2. National Center for Global Health and Medicine, Switzerland
  3. The University of Tokyo, Japan
  4. RIKEN Center for Developmental Biology, Japan
https://doi.org/10.7554/eLife.06328
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Cite this article
  1. Tomomi Hashidate-Yoshida
  2. Takeshi Harayama
  3. Daisuke Hishikawa
  4. Ryo Morimoto
  5. Fumie Hamano
  6. Suzumi M Tokuoka
  7. Miki Eto
  8. Miwa Tamura-Nakano
  9. Rieko Yanobu-Takanashi
  10. Yoshiko Mukumoto
  11. Hiroshi Kiyonari
  12. Tadashi Okamura
  13. Yoshihiro Kita
  14. Hideo Shindou
  15. Takao Shimizu
(2015)
Fatty acyl-chain remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
eLife 4:e06328.
https://doi.org/10.7554/eLife.06328
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  3. Download .RIS

Abstract

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.

Article and author information

Author details

  1. Tomomi Hashidate-Yoshida

    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
    Competing interests
    No competing interests declared.

  2. Takeshi Harayama

    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Switzerland
    Competing interests
    No competing interests declared.

  3. Daisuke Hishikawa

    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
    Competing interests
    No competing interests declared.

  4. Ryo Morimoto

    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
    Competing interests
    Ryo Morimoto, Department of Lipidomics, the University of Tokyo is financially supported by Shimadzu Co., and ONO Phamraceutical Col. Ltd..

  5. Fumie Hamano

    Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    Competing interests
    Fumie Hamano, Department of Lipidomics, the University of Tokyo is financially supported by Shimadzu Co., and ONO Phamraceutical Col. Ltd..

  6. Suzumi M Tokuoka

    Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    Competing interests
    Suzumi M Tokuoka, Department of Lipidomics, the University of Tokyo is financially supported by Shimadzu Co., and ONO Phamraceutical Col. Ltd..

  7. Miki Eto

    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
    Competing interests
    Miki Eto, Department of Lipidomics, the University of Tokyo is financially supported by Shimadzu Co., and ONO Phamraceutical Col. Ltd..

  8. Miwa Tamura-Nakano

    Communal Laboratory, National Center for Global Health and Medicine, Tokyo, Japan
    Competing interests
    No competing interests declared.

  9. Rieko Yanobu-Takanashi

    Department of Laboratory Animal Medicine, National Center for Global Health and Medicine, Tokyo, Japan
    Competing interests
    No competing interests declared.

  10. Yoshiko Mukumoto

    Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan
    Competing interests
    No competing interests declared.

  11. Hiroshi Kiyonari

    Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan
    Competing interests
    No competing interests declared.

  12. Tadashi Okamura

    Department of Laboratory Animal Medicine, National Center for Global Health and Medicine, Tokyo, Japan
    Competing interests
    No competing interests declared.

  13. Yoshihiro Kita

    Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    Competing interests
    Yoshihiro Kita, Department of Lipidomics, the University of Tokyo is financially supported by Shimadzu Co., and ONO Phamraceutical Col. Ltd..

  14. Hideo Shindou

    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
    Competing interests
    No competing interests declared.

  15. Takao Shimizu

    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
    For correspondence
    tshimizu@ri.ncgm.go.jp
    Competing interests
    Takao Shimizu, Department of Lipidomics, the University of Tokyo is financially supported by Shimadzu Co., and ONO Phamraceutical Col. Ltd..

Reviewing Editor

  1. Ben Cravatt, The Scripps Research Institute, United States

Ethics

Animal experimentation: All animal experiments were approved by and performed in accordance with the guidelines of the Animal Research Committee of National Center for Global Health and Medicine (12053, 13009, 14045), and the animal experimentation committee of the University of Tokyo (H09-144, P08-042).

Version history

  1. Received: January 8, 2015
  2. Accepted: April 19, 2015
  3. Accepted Manuscript published: April 21, 2015 (version 1)
  4. Version of Record published: May 19, 2015 (version 2)

Copyright

© 2015, Hashidate-Yoshida et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Tomomi Hashidate-Yoshida
  2. Takeshi Harayama
  3. Daisuke Hishikawa
  4. Ryo Morimoto
  5. Fumie Hamano
  6. Suzumi M Tokuoka
  7. Miki Eto
  8. Miwa Tamura-Nakano
  9. Rieko Yanobu-Takanashi
  10. Yoshiko Mukumoto
  11. Hiroshi Kiyonari
  12. Tadashi Okamura
  13. Yoshihiro Kita
  14. Hideo Shindou
  15. Takao Shimizu
(2015)
Fatty acyl-chain remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
eLife 4:e06328.
https://doi.org/10.7554/eLife.06328

Share this article

https://doi.org/10.7554/eLife.06328

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