Mice lacking lipid droplet-associated hydrolase, a gene linked to human prostate cancer, have normal cholesterol ester metabolism

DC ElementWertSprache
dc.contributor.authorKory, Nora
dc.contributor.authorGrond, Susanne
dc.contributor.authorKamat, Siddhesh S.
dc.contributor.authorLi, Zhihuan
dc.contributor.authorKrahmer, Natalie
dc.contributor.authorChitraju, Chandramohan
dc.contributor.authorZhou, Ping
dc.contributor.authorFrohlich, Florian
dc.contributor.authorSemova, Ivana
dc.contributor.authorEjsing, Christer
dc.contributor.authorZechner, Rudolf
dc.contributor.authorCravatt, Benjamin F.
dc.contributor.authorFarese, Jr., Robert V.
dc.contributor.authorWalther, Tobias C.
dc.date.accessioned2021-12-23T16:24:02Z-
dc.date.available2021-12-23T16:24:02Z-
dc.date.issued2017
dc.identifier.issn00222275
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/14755-
dc.description.abstractVariations in the gene LDAH (C2ORF43), which encodes lipid droplet-associated hydrolase (LDAH), are among few loci associated with human prostate cancer. Homologs of LDAH have been identified as proteins of lipid droplets (LDs). LDs are cellular organelles that store neutral lipids, such as triacylglycerols and sterol esters, as precursors for membrane components and as reservoirs of metabolic energy. LDAH is reported to hydrolyze cholesterol esters and to be important in macrophage cholesterol ester metabolism. Here, we confirm that LDAH is localized to LDs in several model systems. We generated a murine model in which Ldah is disrupted but found no evidence for a major function of LDAH in cholesterol ester or triacylglycerol metabolism in vivo, nor a role in energy or glucose metabolism.(Jlr) Our data suggest that LDAH is not a major cholesterol ester hydrolase, and an alternative metabolic function may be responsible for its possible effect on development of prostate cancer.
dc.description.sponsorshipNational Institues of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01GM097194, R01DK101579]; G. Harold and Leila Y. Mathers Foundation; J. David Gladstone Institute; American Heart AssociationAmerican Heart Association; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [U01HG004085, DK059637, DK020593, DK059635]; CSD Consortium [U01HG004080]; Austrian Science Fund (FWF)Austrian Science Fund (FWF) [W 901, F 3002] Funding Source: researchfish; NATIONAL CENTER FOR RESEARCH RESOURCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [U42RR024244] Funding Source: NIH RePORTER; NATIONAL HUMAN GENOME RESEARCH INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [U01HG004085, U01HG004080] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [P60DK020593, P30DK020593, R01DK101579, U24DK059637, U24DK059635] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM097194] Funding Source: NIH RePORTER; This work was supported by the National Institues of Health Grant 1R01GM097194 (to T.C.W.), Grant R01DK101579 (to R.V.F.), the G. Harold and Leila Y. Mathers Foundation (to T.C.W.), and J. David Gladstone Institute (to R.V.F.). N.K. was supported by an American Heart Association predoctoral fellowship. National Institutes of Health grants to Velocigene at Regeneron Inc. (U01HG004085) and the CSD Consortium (U01HG004080) funded the generation of gene-targeted embryonic stem cells for 8,500 genes in the Knockout Mouse Project (KOMP) and archived and distributed by the KOMP Repository at the University of California, Davis, and Children's Hospital Oakland Research Institute (U42RR024244). Testosterone and corticosterone assays were performed by the Vanderbilt University Medical Center Hormone Assay and Analytical Services Core, which is supported by National Institutes of Health Grants DK059637 and DK020593. T.C.W is an investigator of the Howard Hughes Medical Institute. Dr. Michael Jurczak and the Yale Mouse Metabolic Phenotyping Center were funded by National Institutes of Health Grant DK059635. The content is solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.
dc.language.isoen
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.relation.ispartofJOURNAL OF LIPID RESEARCH
dc.subjectACCUMULATION
dc.subjectACTIVATION
dc.subjectanimal models
dc.subjectBiochemistry & Molecular Biology
dc.subjectBREAST
dc.subjectcholesterol efflux
dc.subjectENZYMES
dc.subjectEXPRESSION
dc.subjectHORMONE-SENSITIVE LIPASE
dc.subjectlipase
dc.subjectlipoprotein metabolism
dc.subjectLOCI
dc.subjectPROTEINS
dc.subjectRISK VARIANTS
dc.subjecttriglycerides
dc.titleMice lacking lipid droplet-associated hydrolase, a gene linked to human prostate cancer, have normal cholesterol ester metabolism
dc.typejournal article
dc.identifier.doi10.1194/jlr.M072538
dc.identifier.isiISI:000392408700019
dc.description.volume58
dc.description.issue1
dc.description.startpage226
dc.description.endpage235
dc.contributor.orcid0000-0001-5307-9021
dc.contributor.orcid0000-0003-4063-7367
dc.contributor.orcid0000-0001-8338-8976
dc.contributor.orcid0000-0003-4963-0276
dc.contributor.orcid0000-0001-5483-1182
dc.contributor.orcid0000-0002-7121-9013
dc.contributor.orcid0000-0001-8307-2189
dc.contributor.orcid0000-0001-6132-7574
dc.contributor.orcid0000-0003-1442-1327
dc.contributor.researcheridAAL-9467-2020
dc.contributor.researcheridQ-6733-2019
dc.contributor.researcheridAAL-3392-2020
dc.contributor.researcheridO-8188-2018
dc.identifier.eissn15397262
dc.publisher.place9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
dcterms.isPartOf.abbreviationJ. Lipid Res.
dcterms.oaStatusGreen Published, hybrid
crisitem.author.deptSonderforschungsbereich 944: Physiologie und Dynamik zellulärer Mikrokompartimente-
crisitem.author.deptidorganisation19-
crisitem.author.orcid0000-0001-8307-2189-
crisitem.author.parentorgFB 05 - Biologie/Chemie-
crisitem.author.grandparentorgUniversität Osnabrück-
crisitem.author.netidFrFl166-
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