期刊
CELL METABOLISM
卷 21, 期 1, 页码 51-64出版社
CELL PRESS
DOI: 10.1016/j.cmet.2014.12.002
关键词
-
资金
- NIH [DK076729, DK088083, DK20579, DK56341, K99 DK094874, RR00954]
Fatty acid synthase (FAS) is altered in metabolic disorders and cancer. Conventional FAS null mice die in utero, so effects of whole-body inhibition of lipogenesis following development are unknown. Inducible global knockout of FAS (iFASKO) in mice was lethal due to a disrupted intestinal barrier and leukopenia. Conditional loss of FAS was associated with the selective suppression of granulopoiesis without disrupting granulocytic differentiation. Transplantation of iFASKO bone marrow into wild-type mice followed by Cre induction resulted in selective neutrophil depletion, but not death. Impaired lipogenesis increased ER stress and apoptosis in neutrophils by preferentially decreasing peroxisome-derived membrane phospholipids containing ether bonds. Inducible global knockout of PexRAP, a peroxisomal enzyme required for ether lipid synthesis, also produced neutropenia. FAS knockdown in neutrophil-like HL-60 cells caused cell loss that was partially rescued by ether lipids. Inhibiting ether lipid synthesis selectively constrains neutrophil development, revealing an unrecognized pathway in immunometabolism.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据