Hepatocyte-specific deletion of lysosomal acid lipase leads to cholesteryl ester but not triglyceride or retinyl ester accumulation.
Animals
CCAAT-Enhancer-Binding Proteins
/ genetics
Cells, Cultured
Cholesterol
/ blood
Cholesterol Esters
/ metabolism
Diet, High-Fat
Diterpenes
/ chemistry
Hepatocytes
/ cytology
Lipids
/ analysis
Liver
/ metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Phospholipids
/ analysis
Sterol Esterase
/ deficiency
Triglycerides
/ metabolism
Vitamin A
/ administration & dosage
cholesterol
hepatocytes
hyperlipidemia, metabolic disorder
lipid metabolism
liver
lysosomal acid lipase
lysosome
neutral lipid ester metabolism
triglyceride
vitamin A
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
07 06 2019
07 06 2019
Historique:
received:
18
12
2018
revised:
23
04
2019
pubmed:
27
4
2019
medline:
26
2
2020
entrez:
27
4
2019
Statut:
ppublish
Résumé
Lysosomal acid lipase (LAL) hydrolyzes cholesteryl ester (CE) and retinyl ester (RE) and triglyceride (TG). Mice globally lacking LAL accumulate CE most prominently in the liver. The severity of the CE accumulation phenotype progresses with age and is accompanied by hepatomegaly and hepatic cholesterol crystal deposition. In contrast, hepatic TG accumulation is much less pronounced in these mice, and hepatic RE levels are even decreased. To dissect the functional role of LAL for neutral lipid ester mobilization in the liver, we generated mice specifically lacking LAL in hepatocytes (hep-LAL-ko). On a standard chow diet, hep-LAL-ko mice exhibited increased hepatic CE accumulation but unaltered TG and RE levels. Feeding the hep-LAL-ko mice a vitamin A excess/high-fat diet (VitA/HFD) further increased hepatic cholesterol levels, but hepatic TG and RE levels in these mice were lower than in control mice. Performing
Identifiants
pubmed: 31023823
pii: S0021-9258(20)35160-7
doi: 10.1074/jbc.RA118.007201
pmc: PMC6556574
doi:
Substances chimiques
CCAAT-Enhancer-Binding Proteins
0
CEBPA protein, mouse
0
Cholesterol Esters
0
Diterpenes
0
Lipids
0
Phospholipids
0
Triglycerides
0
Vitamin A
11103-57-4
Cholesterol
97C5T2UQ7J
Sterol Esterase
EC 3.1.1.13
lysosomal acid lipase, mouse
EC 3.1.1.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9118-9133Subventions
Organisme : Austrian Science Fund FWF
ID : I 3535
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : P 28882
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : W 901
Pays : Austria
Informations de copyright
© 2019 Pajed et al.
Références
Pediatr Endocrinol Rev. 2014 Sep;12 Suppl 1:125-32
pubmed: 25345094
Chem Phys Lipids. 1981 Nov;29(3):235-9
pubmed: 7296725
J Lipid Res. 2008 Aug;49(8):1646-57
pubmed: 18413899
Lancet Gastroenterol Hepatol. 2017 Sep;2(9):670-679
pubmed: 28786388
Hum Mol Genet. 1998 Sep;7(9):1347-54
pubmed: 9700186
J Lipid Res. 1982 Jan;23(1):114-23
pubmed: 7057100
Am J Pathol. 2015 Sep;185(9):2379-89
pubmed: 26212911
Annu Rev Genomics Hum Genet. 2012;13:307-35
pubmed: 22970722
Hum Mol Genet. 2001 Aug 1;10(16):1639-48
pubmed: 11487567
Mol Genet Metab. 2014 Jul;112(3):229-41
pubmed: 24837159
Am J Hum Genet. 2005 Dec;77(6):1061-74
pubmed: 16380916
Diabetologia. 2016 Aug;59(8):1743-52
pubmed: 27153842
J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Mar 1;951-952:119-28
pubmed: 24548922
J Biol Chem. 2016 Aug 19;291(34):17977-87
pubmed: 27354281
Science. 2006 May 5;312(5774):734-7
pubmed: 16675698
Biochem J. 1985 Dec 1;232(2):395-401
pubmed: 4091796
J Biol Chem. 1957 May;226(1):497-509
pubmed: 13428781
Therap Adv Gastroenterol. 2017 Jul;10(7):553-562
pubmed: 28804516
J Hepatol. 2015 Aug;63(2):437-45
pubmed: 25733154
J Hepatol. 2014 Nov;61(5):1135-42
pubmed: 24993530
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Apr;1864(4):500-511
pubmed: 30639734
Eur J Biochem. 1992 Apr 15;205(2):775-84
pubmed: 1315278
J Biol Chem. 2017 Jul 28;292(30):12436-12448
pubmed: 28615446
Curr Chem Genom Transl Med. 2017 Jan 30;11:1-18
pubmed: 28401034
Biochim Biophys Acta. 1993 Oct 13;1170(2):99-108
pubmed: 8399348
Cardiovasc Res. 2013 Sep 1;99(4):674-84
pubmed: 23729663
Biochim Biophys Acta. 1983 May 16;751(3):474-8
pubmed: 6849957
Metabolism. 1981 Aug;30(8):792-7
pubmed: 7266372
J Biol Chem. 1985 Nov 5;260(25):13566-70
pubmed: 2414283
J Lipid Res. 2018 Oct;59(10):1805-1817
pubmed: 30072447
Biochem J. 1957 Mar;65(3):526-33
pubmed: 13412657
Cell Regul. 1990 Aug;1(9):661-74
pubmed: 2150334
J Lipid Res. 2016 Jan;57(1):131-41
pubmed: 26423520
Am J Physiol Lung Cell Mol Physiol. 2004 Apr;286(4):L801-7
pubmed: 14644759
Clin Liver Dis (Hoboken). 2013 Mar 29;2(Suppl 1):S8-S10
pubmed: 30992876
Am J Med. 1968 Apr;44(4):538-46
pubmed: 5642714
Curr Opin Lipidol. 2013 Aug;24(4):332-8
pubmed: 23652569
Int J Mol Sci. 2016 Feb 27;17(3):312
pubmed: 26927097
Prostaglandins Leukot Essent Fatty Acids. 2009 Nov-Dec;81(5-6):313-24
pubmed: 19857945
J Biol Chem. 1985 Dec 5;260(28):15186-93
pubmed: 4066668
J Lipid Res. 1995 Jul;36(7):1498-506
pubmed: 7595074
Biochim Biophys Acta. 1994 May 13;1212(2):176-82
pubmed: 8180243
J Lipid Res. 2001 Apr;42(4):489-500
pubmed: 11290820
J Lipid Res. 1999 Feb;40(2):309-17
pubmed: 9925661
Biochim Biophys Acta. 2015 Jul;1851(7):937-45
pubmed: 25732851
J Hepatol. 2013 Jun;58(6):1230-43
pubmed: 23485521
J Med Chem. 2010 Jul 22;53(14):5281-9
pubmed: 20557099
Am J Physiol Gastrointest Liver Physiol. 2014 Oct 15;307(8):G836-47
pubmed: 25147230
Pediatrics. 1961 Nov;28:742-57
pubmed: 14008104
Biochim Biophys Acta. 1980 Feb 22;617(2):305-17
pubmed: 7357021