title: Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport.
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.
authors.affiliation: Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hashidate-Yoshida
authors.affiliation: Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Harayama
authors.affiliation: Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hishikawa
authors.affiliation: Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Morimoto
authors.affiliation: Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Hamano
authors.affiliation: Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Suzumi M
authors.initials: SM
authors.lastname: Tokuoka
authors.affiliation: Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Eto
authors.affiliation: Communal Laboratory, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Tamura-Nakano
authors.affiliation: Department of Laboratory Animal Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Yanobu-Takanashi
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Mukumoto
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.affiliation: Department of Laboratory Animal Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kita
authors.affiliation: Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Shindou
authors.affiliation: Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis*; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D008099:Liver / Q000166:cytology; D051379:Mice; D010743:Phospholipids / Q000378:metabolism*; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D014280:Triglycerides; D016718:Arachidonic Acid; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C000600794:LPCAT3 protein, mouse
keywords: arachidonic acid; biochemistry; human; lipoproteins; mouse; phospholipids; triacylglycerol