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

Citation
Kory, N., et al. “Mice Lacking Lipid Droplet-Associated Hydrolase, A Gene Linked To Human Prostate Cancer, Have Normal Cholesterol Ester Metabolism.”. Journal Of Lipid Research, pp. 226-235.
Center Vanderbilt University
Author Nora Kory, Susanne Grond, Siddhesh S Kamat, Zhihuan Li, Natalie Krahmer, Chandramohan Chitraju, Ping Zhou, Florian Fröhlich, Ivana Semova, Christer Ejsing, Rudolf Zechner, Benjamin F Cravatt, Robert Farese V, Tobias C Walther
Keywords animal models, Cholesterol efflux, lipase, lipoprotein metabolism, triglycerides
Abstract

Variations 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. 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.

Year of Publication
2017
Journal
Journal of lipid research
Volume
58
Issue
1
Number of Pages
226-235
Date Published
12/2017
ISSN Number
1539-7262
DOI
10.1194/jlr.M072538
Alternate Journal
J. Lipid Res.
PMID
27836991
PMCID
PMC5234725
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