Mice lacking lipid droplet-associated hydrolase, a gene linked to human prostate cancer, have normal cholesterol ester metabolism.
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.
Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA.
Nora
N
Kory
Institute of Molecular Biosciences, University of Graz, Graz, Austria.
Susanne
S
Grond
Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA.|Skaggs Institute for Chemical Biology Scripps Research Institute, La Jolla, CA.
Siddhesh S
SS
Kamat
Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA.
Zhihuan
Z
Li
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
Natalie
N
Krahmer
Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA.
Chandramohan
C
Chitraju
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA.
Ping
P
Zhou
Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA.
Florian
F
Fröhlich
Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA.
Ivana
I
Semova
Department of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense, Denmark.
Christer
C
Ejsing
Institute of Molecular Biosciences, University of Graz, Graz, Austria.
Rudolf
R
Zechner
Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA.|Skaggs Institute for Chemical Biology Scripps Research Institute, La Jolla, CA.
Benjamin F
BF
Cravatt
Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA twalther@hsph.harvard.edu robert@hsph.harvard.edu.|Department of Cell Biology, Harvard Medical School, Boston, MA.|Broad Institute of MIT and Harvard, Cambridge, MA.
Robert V
RV
Farese
Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA twalther@hsph.harvard.edu robert@hsph.harvard.edu.|Department of Cell Biology, Harvard Medical School, Boston, MA.|Broad Institute of MIT and Harvard, Cambridge, MA.|Howard Hughes Medical Institute, Boston, MA.
Tobias C
TC
Walther
D000818:Animals; D002788:Cholesterol Esters / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D057057:Serine Proteases / Q000235:genetics* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D002788:Cholesterol Esters; D014280:Triglycerides; C587070:LD-associated hydrolase, mouse; D057057:Serine Proteases; D005947:Glucose
animal models; cholesterol efflux; lipase; lipoprotein metabolism; triglycerides