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

Year: 2016

Type: article

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.

Source: Journal of Lipid Research

DOI: 10.1194/jlr.m072538

Authors: 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 V. Farese, Tobias C. Walther

Institutions: Harvard University, University of Graz, Scripps Research Institute, Max Planck Institute of Biochemistry, University of California, San Francisco, University of Southern Denmark, Broad Institute, Howard Hughes Medical Institute

Language: English

Topic: Lipid metabolism and biosynthesis

Subfield: Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430

Funders: American Heart Association, G. Harold and Leila Y. Mathers Charitable Foundation, Yale University, Vanderbilt University, Gladstone Institutes, Regeneron Pharmaceuticals, G. Harold and Leila Y. Mathers Foundation, Vanderbilt University Medical Center, National Institutes of Health, University of California, Davis, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources

OpenAlex ID: W2550897360