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

DOI PDF Web Site Web Site XML 26 Citations 63 References Open Access
  • Tomomi Hashidate-Yoshida
    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
  • Takeshi Harayama
    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
  • Daisuke Hishikawa
    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
  • Ryo Morimoto
    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
  • Fumie Hamano
    Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • Suzumi M Tokuoka
    Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • Miki Eto
    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
  • Miwa Tamura-Nakano
    Communal Laboratory, National Center for Global Health and Medicine, Tokyo, Japan
  • Rieko Yanobu-Takanashi
    Department of Laboratory Animal Medicine, National Center for Global Health and Medicine, Tokyo, Japan
  • Yoshiko Mukumoto
    Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan
  • Hiroshi Kiyonari
    Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan
  • Tadashi Okamura
    Department of Laboratory Animal Medicine, National Center for Global Health and Medicine, Tokyo, Japan
  • Yoshihiro Kita
    Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • Hideo Shindou
    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
  • Takao Shimizu
    Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan

Description

<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>

Journal

  • eLife

    eLife 4 e06328-, 2015-04-21

    eLife Sciences Publications, Ltd

Citations (26)*help

See more

References(63)*help

See more

Related Projects

See more

Report a problem

Back to top