CDP-diacylglycerol synthases regulate the growth of lipid droplets and adipocyte development

J Lipid Res. 2016 May;57(5):767-80. doi: 10.1194/jlr.M060574. Epub 2016 Mar 5.

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.

Keywords: SEIPIN; cytidine 5′-diphosphate; lipin-1; peroxisome proliferator-activated receptor γ; phosphatidic acid; phosphatidylcholine; phosphatidylglycerol; phosphatidylinositol; phosphatidylinositol synthase; triacylglycerol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / enzymology*
  • Animals
  • Cell Differentiation
  • Diacylglycerol Cholinephosphotransferase / physiology*
  • Gene Expression
  • HeLa Cells
  • Humans
  • Lipid Droplets / enzymology*
  • Lipid Metabolism
  • Mice
  • Phosphatidate Phosphatase / genetics
  • Phosphatidate Phosphatase / metabolism
  • Phospholipids / metabolism
  • Protein Transport
  • Triglycerides / metabolism

Substances

  • Phospholipids
  • Triglycerides
  • CDS1 protein, human
  • CDS2 protein, human
  • Diacylglycerol Cholinephosphotransferase
  • LPIN1 protein, human
  • Phosphatidate Phosphatase