文章基本信息

标题：CDP-diacylglycerol synthases regulate the growth of lipid droplets and adipocyte development
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作者：Yanfei Qi ; Tamar S. Kapterian ; Ximing Du 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2016
卷号：57
期号：5
页码：767-780
DOI：10.1194/jlr.M060574
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：The expansion of lipid droplets (LDs) and the differentiation of preadipocytes are two important aspects of mammalian lipid storage. In this study, we examined the role of CDP-diacylglycerol (DAG) synthases (CDSs), encoded by CDS1 and CDS2 genes in mammals, in lipid storage. CDS enzymes catalyze the formation of CDP-DAG from phosphatidic acid (PA). Knocking down either CDS1 or CDS2 resulted in the formation of giant or supersized LDs in cultured cells. Moreover, depleting CDS1 almost completely blocked the differentiation of 3T3-L1 preadipocytes, whereas depleting CDS2 had a moderate inhibitory effect on adipocyte differentiation. The levels of many PA species were significantly increased upon knocking down CDS1 . In contrast, only a small number of PA species were increased upon depleting CDS2 . Importantly, the amount of PA in the endoplasmic reticulum was dramatically increased upon knocking down CDS1 or CDS2 . Our results suggest that the changes in PA level and localization may underlie the formation of giant LDs as well as the block in adipogenesis in CDS-deficient cells. We have therefore identified CDS1 and CDS2 as important novel regulators of lipid storage, and these results highlight the crucial role of phospholipids in mammalian lipid storage.
关键词：lipin-1 ; peroxisome proliferator-activated receptor γ ; phosphatidic acid ; phosphatidylcholine ; phosphatidylglycerol ; phosphatidylinositol ; phosphatidylinositol synthase ; SEIPIN ; triacylglycerol ; cytidine 5′-diphosphate