title: Small Intestine but Not Liver Lysophosphatidylcholine Acyltransferase 3 (Lpcat3) Deficiency Has a Dominant Effect on Plasma Lipid Metabolism.
abstract: Lysophosphatidylcholine acyltransferase 3 (Lpcat3) is involved in phosphatidylcholine remodeling in the small intestine and liver. We investigated lipid metabolism in inducible intestine-specific and liver-specificLpcat3gene knock-out mice. We producedLpcat3-Flox/villin-Cre-ER(T2)mice, which were treated with tamoxifen (at days 1, 3, 5, and 7), to deleteLpcat3specifically in the small intestine. At day 9 after the treatment, we found that Lpcat3 deficiency in enterocytes significantly reduced polyunsaturated phosphatidylcholines in the enterocyte plasma membrane and reduced Niemann-Pick C1-like 1 (NPC1L1), CD36, ATP-binding cassette transporter 1 (ABCA1), and ABCG8 levels on the membrane, thus significantly reducing lipid absorption, cholesterol secretion through apoB-dependent and apoB-independent pathways, and plasma triglyceride, cholesterol, and phospholipid levels, as well as body weight. Moreover, Lpcat3 deficiency does not cause significant lipid accumulation in the small intestine. We also utilized adenovirus-associated virus-Cre to depleteLpcat3in the liver. We found that liver deficiency only reduces plasma triglyceride levels but not other lipid levels. Furthermore, there is no significant lipid accumulation in the liver. Importantly, small intestine Lpcat3 deficiency has a much bigger effect on plasma lipid levels than that of liver deficiency. Thus, inhibition of small intestine Lpcat3 might constitute a novel approach for treating hyperlipidemia.
authors.affiliation: From the Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York 11203.
authors.forename: Inamul
authors.initials: I
authors.lastname: Kabir
authors.affiliation: From the Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, the Molecular and Cellular Cardiology Program, Veterans Affairs New York Harbor Healthcare System, Brooklyn, New York 11209.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: the Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana 46285, and.
authors.forename: Hai H
authors.initials: HH
authors.lastname: Bui
authors.affiliation: the Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana 46285, and.
authors.forename: Ming-Shang
authors.initials: MS
authors.lastname: Kuo
authors.affiliation: the Horae Gene Therapy Center and Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Guangping
authors.initials: G
authors.lastname: Gao
authors.affiliation: From the Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, the Molecular and Cellular Cardiology Program, Veterans Affairs New York Harbor Healthcare System, Brooklyn, New York 11209, xjiang@downstate.edu.
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Jiang
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000172:deficiency*; D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity
chemical_list: D008243:1-Acylglycerophosphocholine O-Acyltransferase; D064286:ATP Binding Cassette Transporter 1; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D018955:CD36 Antigens; D008074:Lipoproteins; D026901:Membrane Transport Proteins; C577833:Abca1 protein, mouse; C462601:ABCG8 protein, mouse; C482445:Npc1l1 protein, mouse; C000600794:LPCAT3 protein, mouse
keywords: cholesterol metabolism; gene knockout; lipid absorption; lipoprotein metabolism; lipoprotein secretion; phosphatidylcholine; phospholipid metabolism; triacylglycerol
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