Abstract
Changes in fatty acid (FA) and glycerophospholipid (GPL) metabolism associated with cell cycle entry are not fully understood. In this study FA-GPL remodeling was investigated in resting and proliferating primary human T cells. Significant changes were measured in the composition and distribution of FAs in GPLs following receptor activation of human T cells. The FA distribution of proliferating T cells was very similar to that of the human Jurkat T cell line and when the stimulus was removed from proliferating T cells, they stopped proliferating and the FA distribution largely reverted back to that of resting T cells. The cellular content of saturated and monounsaturated FAs was significantly increased in proliferating cells, which was associated with an induction of FA synthase and stearoyl-CoA desaturase-1 gene expression. Additionally, cellular arachidonate was redistributed in GPLs in a distinct pattern that was unlike any other FAs. This redistribution was associated with an induction of CoA-dependent and CoA-independent remodeling. Accordingly, significant changes in the expression of several acyl-CoA synthetases, lysophospholipid acyltransferases, and phospholipase A2 were measured. Overall, these results suggest that metabolic pathways are activated in proliferating T cells that may represent fundamental changes associated with human cell proliferation.
Highlights
Changes in fatty acid (FA) and glycerophospholipid (GPL) metabolism associated with cell cycle entry are not fully understood
During membrane biogenesis associated with cell proliferation, FA biosynthesis is enhanced and the FAs incorporated into positions sn-1 and sn-2 of phosphatidic acid during de novo biosynthesis of GPLs (Kennedy pathway) are generally saturated FAs (SFAs) and monounsaturated FAs (MUFAs) [2]
Because de novo FA synthesis is known to accompany cell proliferation, the increase in SFA mass in proliferating T cells was not surprising [53], important changes in the unsaturated fatty acyl content of GPLs were measured and these may be the result of fundamental processes associated with cell proliferation
Summary
Changes in fatty acid (FA) and glycerophospholipid (GPL) metabolism associated with cell cycle entry are not fully understood. Similar results were obtained when lipid phosphorous associated with the different GPL classes was measured in resting and proliferating T cells (supplementary Fig. II).
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