Contrasting the incorporation of glycerol into lipids caused by the presence of two isoforms of diacylglycerol kinase (605.20)

Abstract

The mammalian isoforms of diacylglycerol kinase (DGK) include the epsilon isoform (DGKε) and the delta isoform (DGKδ). DGKε has specificity for substrates with an arachidonoyl group, while DGKδ shows no acyl chain specificity for the substrate, but it promotes fatty acid synthesis resulting in an increased fraction of lipids with shorter and less unsaturated acyl chains. We have compared the effects of knocking out each of these isoforms individually using SV40 transformed mouse embryo fibroblasts (MEFs). We compared wild‐type (WT) MEFs with those from knock‐out (KO) mice. We find that DGKδ‐KO MEFs have lower incorporation of 3H‐glycerol into lipids compared with their WT counterparts. This is consistent with our recent demonstration (Biochemistry (2013) 52, 7766) that the depletion of this DGK isoform results in less fatty acid synthesis. This change is not caused by a decreased expression of glycerol kinase in the KO cells. In contrast, the DGKε‐KO MEFs show greater incorporation of 3H‐glycerol into lipids compared with their WT counterparts, with no change in the relative amounts of various lipids between the DGKε‐KO and WT MEFs. This result is explained by our observation that glycerol kinase is more highly expressed in the DGKε‐KO cells than in their WT counterparts.