title: CDP-diacylglycerol synthases regulate the growth of lipid droplets and adipocyte development.
abstract: 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.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Qi
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia.
authors.forename: Tamar S
authors.initials: TS
authors.lastname: Kapterian
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia.
authors.forename: Ximing
authors.initials: X
authors.lastname: Du
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia.
authors.forename: Qianli
authors.initials: Q
authors.lastname: Ma
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia.
authors.forename: Weihua
authors.initials: W
authors.lastname: Fei
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Huang
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia.
authors.forename: Ian W
authors.initials: IW
authors.lastname: Dawes
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia h.rob.yang@unsw.edu.au.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Yang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000201:enzymology*; D000818:Animals; D002454:Cell Differentiation; D002798:Diacylglycerol Cholinephosphotransferase / Q000502:physiology*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D066292:Lipid Droplets / Q000201:enzymology*; D050356:Lipid Metabolism; D051379:Mice; D010711:Phosphatidate Phosphatase / Q000235:genetics / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D021381:Protein Transport; D014280:Triglycerides / Q000378:metabolism
chemical_list: D010743:Phospholipids; D014280:Triglycerides; C000622211:CDS1 protein, human; C000622212:CDS2 protein, human; D002798:Diacylglycerol Cholinephosphotransferase; C485999:LPIN1 protein, human; D010711:Phosphatidate Phosphatase
keywords: SEIPIN; cytidine 5′-diphosphate; lipin-1; peroxisome proliferator-activated receptor γ; phosphatidic acid; phosphatidylcholine; phosphatidylglycerol; phosphatidylinositol; phosphatidylinositol synthase; triacylglycerol