title: Lysophospholipid acyltransferases mediate phosphatidylcholine diversification to achieve the physical properties required in vivo.
abstract: The acyl-chain composition of the major mammalian phospholipid phosphatidylcholine (PC) is distinct in various tissues. Although it was classically suggested that PC diversity is acquired through acyl-chain remodeling, the mechanisms and biological relevance of acyl-chain diversity remain unclear. Here, we show that differences in the substrate selectivity of lysophospholipid acyltransferases regulate tissue PC acyl-chain composition through contribution of both the de novo and remodeling pathways, depending on the fatty acid species. Unexpectedly, while dipalmitoyl-PC (DPPC) is enriched through the remodeling pathway, several polyunsaturated PC molecules accumulate during the de novo pathway. We confirmed this concept for DPPC in pulmonary surfactant and showed that the biophysical properties of this lipid are important to prevent the early onset of acute lung injury. We propose a model of harmonized processes for phospholipid diversification to satisfy in vivo requirements, with an example of its biological relevance.
authors: Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan.
authors: Takeshi
authors: T
authors: Harayama
authors: Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan; Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Miki
authors: M
authors: Eto
authors: Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan.
authors: Hideo
authors: H
authors: Shindou
authors: Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Yoshihiro
authors: Y
authors: Kita
authors: Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan; Advanced Medical Research Department, Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Kanagawa 227-0033, Japan.
authors: Eiji
authors: E
authors: Otsubo
authors: Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan.
authors: Daisuke
authors: D
authors: Hishikawa
authors: Department of Immunology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan.
authors: Satoshi
authors: S
authors: Ishii
authors: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors: Kenji
authors: K
authors: Sakimura
authors: Brain Science Laboratory, The Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.
authors: Masayoshi
authors: M
authors: Mishina
authors: Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan; Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: tshimizu@ri.ncgm.go.jp.
authors: Takao
authors: T
authors: Shimizu
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000032:analysis / Q000378:metabolism; D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D055370:Lung Injury / Q000209:etiology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010713:Phosphatidylcholines / Q000032:analysis / Q000378:metabolism*; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D018925:Chemokines; D016207:Cytokines; D010713:Phosphatidylcholines; D013501:Surface-Active Agents; D015060:1,2-Dipalmitoylphosphatidylcholine; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C028694:1-palmitoyl-2-oleoylphosphatidylcholine