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

被引:16
作者
Kory, Nora [1 ]
Grond, Susanne [2 ]
Kamat, Siddhesh S. [3 ,4 ,11 ]
Li, Zhihuan [1 ]
Krahmer, Natalie [5 ]
Chitraju, Chandramohan [1 ]
Zhou, Ping [6 ]
Frohlich, Florian [1 ,12 ]
Semova, Ivana [1 ]
Ejsing, Christer [7 ]
Zechner, Rudolf [2 ]
Cravatt, Benjamin F. [3 ,4 ]
Farese, Robert V., Jr. [1 ,8 ,9 ]
Walther, Tobias C. [1 ,8 ,9 ,10 ]
机构
[1] Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA
[2] Graz Univ, Inst Mol Biosci, Graz, Austria
[3] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
[4] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[5] Max Planck Inst Biochem, Dept Prote & Signal Transduct, Martinsried, Germany
[6] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA
[7] Univ Southern Denmark, Dept Biochem & Mol Biol, Villum Ctr Bioanalyt Sci, Odense, Denmark
[8] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA
[9] Broad Inst MIT & Harvard, Cambridge, MA USA
[10] Howard Hughes Med Inst, Boston, MA 02115 USA
[11] Indian Inst Sci Educ & Res, Dept Biol & Chem, Pune, Maharashtra, India
[12] Univ Osnabruck, Mol Membrane Biol Sect, Dept Biol Chem, Osnabruck, Germany
基金
美国国家卫生研究院;
关键词
lipase; lipoprotein metabolism; cholesterol efflux; triglycerides; animal models; HORMONE-SENSITIVE LIPASE; RISK VARIANTS; PROTEINS; EXPRESSION; BREAST; ACCUMULATION; ACTIVATION; ENZYMES; LOCI;
D O I
10.1194/jlr.M072538
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.(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.
引用
收藏
页码:226 / 235
页数:10
相关论文
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