Effect of liver total sphingomyelin synthase deficiency on plasma lipid metabolism.
Albumin-Cre recombinase
Glycosphingolipids
High-density lipoprotein
Sms1 liver-specific/ Sms2 global knockout mice
Sphingomyelin
Very low-density lipoprotein
Journal
Biochimica et biophysica acta. Molecular and cell biology of lipids
ISSN: 1879-2618
Titre abrégé: Biochim Biophys Acta Mol Cell Biol Lipids
Pays: Netherlands
ID NLM: 101731727
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
30
10
2020
revised:
11
01
2021
accepted:
28
01
2021
pubmed:
6
2
2021
medline:
30
6
2021
entrez:
5
2
2021
Statut:
ppublish
Résumé
Sphingomyelin (SM) is one major phospholipids on lipoproteins. It is enriched on apolipoprotein B-containing particles, including very low-density lipoprotein (VLDL) and its catabolites, low-density lipoprotein (LDL). SM is synthesized by sphingomyelin synthase 1 and 2 (SMS1 and SMS2) which utilizes ceramide and phosphatidylcholine, as two substrates, to produce SM and diacylglyceride. SMS1 and SMS2 activities are co-expressed in all tested tissues, including the liver where VLDL is produced. Thus, neither Sms1 gene knockout (KO) nor Sms2 KO approach is sufficient to evaluate the effect of SMS on VLDL metabolism. We prepared liver-specific Sms1 KO/global Sms2 KO mice to evaluate the effect of hepatocyte SM biosynthesis in lipoprotein metabolism. We found that hepatocyte total SMS depletion significantly reduces cellular sphingomyelin levels. Also, we found that the deficiency induces cellular glycosphingolipid levels which is specifically related with SMS1 but not SMS2 deficiency. To our surprise, hepatocyte total SMS deficiency has marginal effect on hepatocyte ceramide, diacylglyceride, and phosphatidylcholine levels. Importantly, total SMS deficiency decreases plasma triglyceride but not apoB levels and reduces larger VLDL concentration. The reduction of triglyceride levels also was observed when the animals were on a high fat diet. Our results show that hepatocyte total SMS blocking can reduce VLDL-triglyceride production and plasma triglyceride levels. This phenomenon could be related with a reduction of atherogenicity.
Identifiants
pubmed: 33545384
pii: S1388-1981(21)00024-X
doi: 10.1016/j.bbalip.2021.158898
pmc: PMC8022321
mid: NIHMS1684271
pii:
doi:
Substances chimiques
Membrane Lipids
0
Sgms1 protein, mouse
EC 2.7.8.-
Transferases (Other Substituted Phosphate Groups)
EC 2.7.8.-
Sgms2 protein, mouse
EC 2.7.8.27
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
158898Subventions
Organisme : BLRD VA
ID : I01 BX000900
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139582
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149730
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.
Références
J Clin Invest. 1996 Sep 15;98(6):1455-64
pubmed: 8823312
Cell. 1992 Oct 16;71(2):343-53
pubmed: 1423598
J Biol Chem. 2005 May 6;280(18):18336-40
pubmed: 15734742
Arterioscler Thromb. 1991 Nov-Dec;11(6):1795-805
pubmed: 1931881
Arterioscler Thromb Vasc Biol. 2012 Jul;32(7):1577-84
pubmed: 22580896
Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1519-26
pubmed: 18566297
Primates Med. 1976;9:145-223
pubmed: 174070
Dalton Trans. 2009 Jun 7;(21):4129-35
pubmed: 19452061
J Biol Chem. 1961 May;236:1264-8
pubmed: 13728665
Biochim Biophys Acta. 2005 Oct 15;1737(1):44-51
pubmed: 16216550
Hepatology. 2016 Dec;64(6):2089-2102
pubmed: 27642075
Hum Mol Genet. 1993 Dec;2(12):2109-16
pubmed: 8111381
Arterioscler Thromb Vasc Biol. 2009 Jun;29(6):850-6
pubmed: 19286635
J Biol Chem. 2015 Mar 27;290(13):8196-205
pubmed: 25638820
Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2114-20
pubmed: 20814016
J Lipid Res. 1967 Nov;8(6):676-81
pubmed: 6057496
Gastroenterol Hepatol (N Y). 2013 Sep;9(9):605-6
pubmed: 24729773
J Biol Chem. 1998 Jan 30;273(5):2738-46
pubmed: 9446580
Atherosclerosis. 2019 Jun;285:147-152
pubmed: 31054484
Nutr Metab (Lond). 2016 May 17;13:36
pubmed: 27190545
Science. 1992 Nov 6;258(5084):999-1001
pubmed: 1439810
J Biol Chem. 2004 Apr 30;279(18):18688-93
pubmed: 14976195
J Lipid Res. 1964 Apr;5:225-31
pubmed: 14174009
Curr Opin Lipidol. 1998 Oct;9(5):471-4
pubmed: 9812202
Arterioscler Thromb Vasc Biol. 1995 May;15(5):551-61
pubmed: 7749869
Gastroenterology. 2015 Nov;149(6):1519-29
pubmed: 26226572
J Biol Chem. 2011 Aug 12;286(32):28544-55
pubmed: 21669879
Biochim Biophys Acta. 1983 Dec 20;754(3):284-91
pubmed: 6652105
Nat Med. 2001 Jul;7(7):847-52
pubmed: 11433351
EMBO J. 2004 Jan 14;23(1):33-44
pubmed: 14685263
PLoS One. 2015 Aug 10;10(8):e0135228
pubmed: 26258408
Circulation. 1990 Nov;82(5):1574-94
pubmed: 1977530
J Biol Chem. 1997 May 9;272(19):12272-8
pubmed: 9139669
Atherosclerosis. 1976 Jan-Feb;23(1):73-83
pubmed: 233765
Circulation. 2007 Oct 16;116(16):1832-44
pubmed: 17938300
Biochim Biophys Acta. 2016 Aug;1861(8 Pt A):688-702
pubmed: 27151272
J Biol Chem. 1998 Feb 27;273(9):5196-203
pubmed: 9478974
Lancet. 1960 Apr 9;1(7128):799-803
pubmed: 13831944
Int J Mol Sci. 2014 Dec 15;15(12):23283-93
pubmed: 25517033
J Biol Chem. 2009 Sep 25;284(39):27010-9
pubmed: 19648608
Biochem Soc Trans. 2000 Feb;28(2):150-4
pubmed: 10816117
PLoS One. 2014 Jul 17;9(7):e102641
pubmed: 25032960
J Biol Chem. 1994 Oct 14;269(41):25879-88
pubmed: 7929292
J Biol Chem. 2018 Nov 9;293(45):17505-17522
pubmed: 30242129
Nutr Metab (Lond). 2006 Jan 05;3:5
pubmed: 16396678
Trends Endocrinol Metab. 2015 Oct;26(10):538-550
pubmed: 26412155
J Lipid Res. 1995 Mar;36(3):395-406
pubmed: 7775852
Arterioscler Thromb Vasc Biol. 2016 Jun;36(6):1132-40
pubmed: 27055903
Mol Cell Biol. 2011 Oct;31(20):4205-18
pubmed: 21844222
Ann N Y Acad Sci. 1985;454:183-94
pubmed: 3865607
Science. 1992 Oct 16;258(5081):468-71
pubmed: 1411543
Arterioscler Thromb Vasc Biol. 2013 Jul;33(7):1513-20
pubmed: 23640498
J Clin Invest. 1998 Feb 15;101(4):905-12
pubmed: 9466986
Annu Rev Biochem. 1981;50:733-64
pubmed: 7023369
Arterioscler Thromb Vasc Biol. 1996 Jan;16(1):4-11
pubmed: 8548424
Arterioscler Thromb Vasc Biol. 2000 Dec;20(12):2614-8
pubmed: 11116061
J Biol Chem. 2011 Feb 4;286(5):3992-4002
pubmed: 21115496
Am J Cardiovasc Dis. 2013;3(1):17-26
pubmed: 23459228
J Nutr Biochem. 2001 Oct;12(10):602-607
pubmed: 12031266
Biochem Biophys Res Commun. 2017 Jan 8;482(2):202-207
pubmed: 27836537