Disclosure: The authors declared no conflict of interest.
Knockdown of diacylglycerol kinase delta inhibits adipocyte differentiation and alters lipid synthesis
Version of Record online: 23 MAY 2013
Copyright © 2013 The Obesity Society
Volume 21, Issue 9, pages 1823–1829, September 2013
How to Cite
Lowe, C. E., Zhang, Q., Dennis, R. J., Aubry, E. M., O'Rahilly, S., Wakelam, M. J.O. and Rochford, J. J. (2013), Knockdown of diacylglycerol kinase delta inhibits adipocyte differentiation and alters lipid synthesis. Obesity, 21: 1823–1829. doi: 10.1002/oby.20297
- Issue online: 23 SEP 2013
- Version of Record online: 23 MAY 2013
- Accepted manuscript online: 2 JAN 2013 07:15PM EST
- Manuscript Accepted: 29 NOV 2012
- Manuscript Received: 21 NOV 2012
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).
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.
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.