Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
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
Affiliations
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; Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Fumie Hamano
Department 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, 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; Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, 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; Section of Animal Models, Department of Infectious Diseases, National Center for Global Health and Medicine, Tokyo, Japan
Yoshihiro Kita
Department 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, Japan
Hideo Shindou
Department 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, Japan
Takao Shimizu
Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan; Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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.
