Journal
CELL METABOLISM
Volume 23, Issue 5, Pages 930-944Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2016.04.001
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Funding
- Wellcome Trust [094143/Z/10/Z]
- European Research Council (LipidArrays)
- NIH [U54HL117798]
- Cardiff University Research Opportunities Programme (CUROP)
- UAB School of Medicine for the Blue Sky Award
- British Heart Foundation [FS/15/45/31603] Funding Source: researchfish
- Wellcome Trust [094143/Z/10/Z] Funding Source: Wellcome Trust
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Human platelets acutely increase mitochondrial energy generation following stimulation. Herein, a lipidomic circuit was uncovered whereby the substrates for this are exclusively provided by cPLA(2), including multiple fatty acids and oxidized species that support energy generation via beta-oxidation. This indicates that acute lipid membrane remodeling is required to support energetic demands during platelet activation. Phospholipase activity is linked to energy metabolism, revealing cPLA(2) as a central regulator of both lipidomics and energy flux. Using a lipidomic approach (LipidArrays), we also estimated the total number of lipids in resting, thrombin-activated, and aspirinized platelets. Significant diversity between genetically unrelated individuals and a wealth of species was revealed. Resting platelets demonstrated similar to 5,600 unique species, with only similar to 50% being putatively identified. Thrombin elevated similar to 900 lipids >2-fold with 86% newly appearing and 45% inhibited by aspirin supplementation, indicating COX-1 is required for major activation-dependent lipidomic fluxes. Many lipids were structurally identified. With similar to 50% of the lipids being absent from databases, a major opportunity for mining lipids relevant to human health and disease is presented.
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