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 PMID:27836991  

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

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
Journal of lipid research | 2017

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.

Pubmed ID: 27836991

Research resources used in this publication

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Associated grants

  • Agency: NCRR NIH HHS, United States
    Id: U42 RR024244
  • Agency: NIDDK NIH HHS, United States
    Id: P60 DK020593
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM097194
  • Agency: NIDDK NIH HHS, United States
    Id: U24 DK059635
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK101579
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK020593
  • Agency: NHGRI NIH HHS, United States
    Id: U01 HG004080
  • Agency: NHGRI NIH HHS, United States
    Id: U01 HG004085
  • Agency: NIDDK NIH HHS, United States
    Id: U24 DK059637

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National Mouse Metabolic Phenotyping Centers (tool)

RRID:SCR_008997

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International Mouse Phenotyping Consortium (IMPC) (tool)

RRID:SCR_006158

Center that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.

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