We have studied the relationship between diacylglycerol kinase delta (DGKδ) and lipogenesis. There is a marked increase in the expression of DGKδ during the differentiation of 3T3-L1 cells to adipocytes, as well as in the synthesis of neutral and polar lipids. When 3T3-L1 undifferentiated fibroblasts are transfected to express DGKδ there is increased triglyceride synthesis without differentiation to adipocytes. Hence, expression of DGKδ promotes lipogenesis. Lipid synthesis is decreased in DGKδ knockout mouse embryo fibroblasts, especially for lipids with shorter acyl chains and limited unsaturation. This reduction occurs for both neutral and polar lipids. These findings suggest reduced de novo lipid synthesis. This is confirmed by measuring the incorporation of glycerol into polar and neutral lipids that is higher in the wild type cells than in the DGKδ knockouts. In comparison, there was no change in lipid synthesis in DGKε knockout mouse embryo fibroblasts. We also demonstrate that the DGKδ knockout cells had a lower expression of acetyl-CoA carboxylase and fatty acid synthase as well as a lower degree of activation by phosphorylation of ATP citrate lyase. These three enzymes are involved in the synthesis of long chain fatty acids. Our results demonstrate that DGKδ markedly increases lipid synthesis, at least in part as a result of promoting the de novo synthesis of fatty acids.

While several studies have highlighted the global shortages of oncologists and their workload, few have studied the characteristics of current oncology training. In this study, an online survey was distributed through a snowball method for cancer care providing physicians in 57 countries. Countries were classified into low-or lower-middle-income countries (LMICs), upper-middle-income countries (UMICs) and high-income countries (HICs) based on World Bank criteria. A total of 273 physicians who were trained in 57 different countries responded to the survey: 33% (90/273), 32% (87/273) and 35% (96/273) in LMICs, UMICs and HICs, respectively. About 60% of respondents were practising physicians and 40% were in training. The proportion of responding trainees was higher in LMICs (51%; 45/89) and UMICs (42%; 37/84), than HICs (19%; 28/96; p = 0.013). A higher proportion of respondents from LMICs (37%; 27/73) self-fund their core oncology training compared to UMICs (13%; 10/77) and HICs (11%; 10/89; p < 0.001). Respondents from HICs were more likely to complete an accepted abstract, poster and publication from their research activities compared to respondents from UMICs and LMICs. Respondents identified several barriers to effective training, including skewed service to education ratio and burnout. With regard to preparedness for practice, mean scores on a 5-point Likert scale were low for professional tasks like supervision and mentoring of trainees, leadership and effective management of an oncology practice and understanding of healthcare systems irrespective of country grouping. In conclusion, the investment in training by the public sector is vital to decreasing the prevalence of self-funding in LMICs. Gaps in research training and enhancement of competencies in research dissemination in LMICs require attention. The instruction on cancer care systems and leadership needs to be incorporated in training curricula in all countries.

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10526 Background: While several studies have highlighted the global shortages of oncologists and their workload, few have studied the characteristics of current oncology training. Methods: An online survey was distributed through a snowball method via national oncology societies and a pre-existing network of contacts to cancer care providing physicians in 57 countries. Countries were classified into low- or lower-middle-income countries (LMICs), upper-middle-income countries (UMICs), and high-income countries (HICs) based on World Bank criteria. Results: 273 physicians who trained in 57 different countries responded to the survey; 33% (90/273), 32% (87/273), and 35% (96/273) in LMICs, UMICs and HICs respectively. 60% of respondents were practicing physicians and 40% were in training. The proportion of trainees was higher in LMICs (51%; 45/89) and UMICs (42%; 37/84), than HICs (19%; 28/96; P = 0.013). A higher proportion of respondents from LMICs (37%; 27/73) self-fund their core oncology training compared to UMICs (13%; 10/77) and HICs (11%; 10/89; P < 0.001). Respondents from HICs were more likely to complete an accepted abstract, poster and publication from their research activities compared to respondents from UMICs and LMICs (abstract: 37/72 (51%) from HICs, 18/66 (27%) from UMICs, 24/65 (37%) from LMICs, P = 0.014; poster: (42/72 (58%) from HICs, 28/66 (42%) from UMICs, 13/65 (20%) from LMICs, P < 0.001; publication: 43/72 (60%) from HICs, 32/66 (49%) from UMICs, 24/65 (37%) from LMICs, P = 0.029). Respondents identified several barriers to effective training including skewed service to education ratio and burnout. With regards to preparedness for practice, mean scores on a 5-point Likert scale were low for professional tasks like supervision and mentoring of trainees, leadership and effective management of an oncology practice, and understanding of healthcare systems irrespective of country grouping. Conclusions: Investment in training by the public sector would be vital to decreasing the prevalence of self-funding in LMIC. Gaps in research training and enhancement of competencies in research dissemination in LMIC require attention. Instruction on cancer care systems and leadership need to be incorporated in training curricula in both LMICs and HICs.

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.