title: Macrophage lipoprotein lipase modulates the development of atherosclerosis but not adiposity.
abstract: The role of macrophage lipoprotein lipase (LpL) in the development of atherosclerosis and adiposity was examined in macrophage LpL knockout (MLpLKO) mice. MLpLKO mice were generated using cre-loxP gene targeting. Loss of LpL in macrophages did not alter plasma LpL activity or lipoprotein levels. Incubation of apolipoprotein E (ApoE)-deficient β-VLDL with peritoneal macrophages from ApoE knockout mice lacking macrophage LpL (MLpLKO/ApoEKO) led to less cholesteryl ester formation than that found with ApoEKO macrophages. MLpLKO/ApoEKO macrophages had reduced intracellular triglyceride levels, with decreased CD36 and carnitine palmitoyltransferase-1 mRNA levels compared with ApoEKO macrophages, when incubated with VLDL. Although both MLpLKO/ApoEKO and ApoEKO mice developed comparable hypercholesterolemia in response to feeding with a Western-type diet for 12 weeks, atherosclerosis was less in MLpLKO/ApoEKO mice. Epididymal fat mass and gene expression levels associated with inflammation did not differ between the two groups. In conclusion, macrophage LpL plays an important role in the development of atherosclerosis but not adiposity.
authors: Department of Medicine, Jichi Medical University, Tochigi 329-0498, Japan.
authors: Manabu
authors: M
authors: Takahashi
authors: Hiroaki
authors: H
authors: Yagyu
authors: Fumiko
authors: F
authors: Tazoe
authors: Shuichi
authors: S
authors: Nagashima
authors: Taichi
authors: T
authors: Ohshiro
authors: Kenta
authors: K
authors: Okada
authors: Jun-ichi
authors: J
authors: Osuga
authors: Ira J
authors: IJ
authors: Goldberg
authors: Shun
authors: S
authors: Ishibashi
mesh_terms: D050154:Adiposity / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015152:Blotting, Northern; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology*; D017737:Macrophages, Peritoneal / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001057:Apolipoproteins E; D002334:Carnitine O-Palmitoyltransferase; D008071:Lipoprotein Lipase
references: Atherosclerosis. 1996 Jul;124(1):1-8
references: 8800489
references: Obesity (Silver Spring). 2007 Nov;15(11):2595-604
references: 18070750
references: Atherosclerosis. 1987 Dec;68(3):231-40
references: 3426656
references: J Biol Chem. 2010 Jun 25;285(26):20192-201
references: 20424161
references: J Biol Chem. 2000 Oct 20;275(42):32523-9
references: 10913136
references: Curr Opin Lipidol. 1999 Apr;10(2):97-105
references: 10327277
references: J Biol Chem. 2004 Jun 11;279(24):25050-7
references: 15028738
references: J Clin Invest. 2000 Apr;105(8):1049-56
references: 10772649
references: Transgenic Res. 1999 Aug;8(4):265-77
references: 10621974
references: Horm Res. 2000;54(5-6):275-80
references: 11595817
references: J Clin Invest. 1992 Oct;90(4):1504-12
references: 1401083
references: J Lipid Res. 1996 Apr;37(4):693-707
references: 8732771
references: J Clin Invest. 1999 Jun;103(12):1697-705
references: 10377176
references: J Clin Invest. 2003 Feb;111(3):419-26
references: 12569168
references: J Biol Chem. 2000 Aug 25;275(34):26293-9
references: 10858435
references: J Lipid Res. 2002 May;43(5):805-14
references: 11971952
references: Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):E53-62
references: 10978269
references: Cell. 2012 Sep 28;151(1):138-52
references: 23021221
references: Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7242-6
references: 8692976
references: J Clin Invest. 2005 Aug;115(8):2192-201
references: 16075060
references: J Lipid Res. 1995 Nov;36(11):2320-8
references: 8656070
references: Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10261-6
references: 9294198
references: Nat Med. 2009 Dec;15(12):1383-91
references: 19966778
references: J Clin Invest. 2003 Dec;112(12):1821-30
references: 14679177
references: FASEB J. 2005 Nov;19(13):1869-71
references: 16123174
references: J Biol Chem. 2010 Dec 10;285(50):39239-48
references: 20889497
references: Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2062-8
references: 16123319
references: Curr Opin Lipidol. 2009 Oct;20(5):379-85
references: 19625959
references: J Biol Chem. 2000 Jul 14;275(28):21324-30
references: 10777503
references: Comp Biochem Physiol B Biochem Mol Biol. 1998 Oct;121(2):201-12
references: 9972295
references: Proc Natl Acad Sci U S A. 2011 May 10;108(19):7980-4
references: 21518912
references: J Biol Chem. 1990 Feb 25;265(6):3040-7
references: 2303437
references: Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8342-6
references: 1656440
references: J Biol Chem. 1993 Sep 25;268(27):20419-32
references: 8376399
references: J Lipid Res. 1999 Sep;40(9):1677-85
references: 10484615
references: Arteriosclerosis. 1983 Sep-Oct;3(5):433-40
references: 6626033
references: Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1421-8
references: 18451332
references: Cardiovasc Res. 2007 Feb 1;73(3):470-80
references: 17084825
references: J Clin Invest. 1997 Aug 1;100(3):649-57
references: 9239412
references: J Lipid Res. 2006 Jul;47(7):1406-15
references: 16639077
references: Circ J. 2010 Feb;74(2):213-20
references: 20065609
references: J Clin Invest. 2003 Dec;112(12):1796-808
references: 14679176
references: J Clin Invest. 1993 Jul;92(1):411-7
references: 8326009
references: Curr Opin Lipidol. 1994 Apr;5(2):117-25
references: 8044414
references: J Biol Chem. 2005 Jun 10;280(23):21763-72
references: 15826936
references: Diabetes. 1995 Apr;44(4):414-7
references: 7698509