Knockdown of diacylglycerol kinase delta inhibits adipocyte differentiation and alters lipid synthesis

Christopher E Lowe, Qifeng Zhang, Rowena J Dennis, Evelyne M Aubry, Stephen O'Rahilly, Michael J O Wakelam, Justin J Rochford

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objective: Decreased expression of diacylglycerol kinase delta (DGKδ) has been linked to insulin resistance in humans and mice and it is abundantly expressed in adipose tissue. Therefore, its role in adipogenesis was examined. Design and Methods: 3T3-L1 pre-adipocytes were generated in which DGKδ expression had been knocked down and the effect of this on adipogenesis was determined. Lipidomic analyses were performed to determine levels of the DGKδ product phosphatidic acid (PA), its substrate diacylglycerol (DAG) and triglyceride (TG). Results: Inhibiting DGKδ expression prevents adipogenesis. DGKδ knockdown in differentiating adipocytes blunted the increase in total levels of PA and DAG but did not affect the early rise in TG levels. DAG or PA species acting as TG precursors were only modestly reduced by DGKδ knockdown which significantly impaired the accumulation of DAG or PA species implicated in intracellular signaling. The DAG activated kinase PKCδ was also stimulated in DGKδ knockdown cells, despite no increase in detectable species of DAG. Conclusions: DGKδ is a novel regulator of adipogenesis and phosphorylates a quantitatively small pool of signaling DAG important for differentiation and indirectly affects overall levels of signaling DAG and PA species distinct from those acting as precursors for TG synthesis.
Original languageEnglish
Pages (from-to)1823-1829
Number of pages7
JournalObesity
Volume21
Issue number9
Early online date23 May 2013
DOIs
Publication statusPublished - Sep 2013

Keywords

  • 3T3-L1 Cells
  • Adipocytes
  • Adipogenesis
  • Adipose Tissue
  • Animals
  • Diacylglycerol Kinase
  • Diglycerides
  • Gene Knockdown Techniques
  • Humans
  • Lipogenesis
  • Mice
  • Phosphatidic Acids
  • Phosphorylation
  • Signal Transduction
  • Triglycerides

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    Lowe, C. E., Zhang, Q., Dennis, R. J., Aubry, E. M., O'Rahilly, S., Wakelam, M. J. O., & Rochford, J. J. (2013). Knockdown of diacylglycerol kinase delta inhibits adipocyte differentiation and alters lipid synthesis. Obesity, 21(9), 1823-1829. https://doi.org/10.1002/oby.20297