Abstract Number: PB0859
Meeting: ISTH 2022 Congress
Background: As platelets circulate in the blood, they require the mitochondrial oxidation of glucose and fatty acids (FA) to meet the energy demands of survival and vascular surveillance. There is a basic understanding of glucose utilisation in platelets, where on activation they adopt a glycolytic phenotype. However, little is currently known about the uptake and metabolic processing of FA.
Aims: We sought to understand exogenous FA uptake, trafficking and utilisation in blood platelets, and to study downstream effects on platelet metabolism and biology.
Methods: We used a combination of fluorescent flow cytometry (FFC), confocal laser scanning microscopy (CLSM) and bioenergetic measurements to profile the platelets in response to FA.
Results: Measuring platelet uptake of FA by FFC with the FA analogue BODIPY™ 558/568 C12 led to a concentration-dependent increase in uptake, which was reduced in response to platelet activation. Using CLSM it was observed FA accumulated within the cells and were co-localised with mitochondrial markers TOMM22 or MitoTracker™ Deep Red. Having established that FA were internalised and trafficked under quiescent conditions we used the C16 FA palmitate to profile metabolic function. Treatment of platelets with palmitate in the presence of tetramethylrhodamine ethyl ester, a marker of mitochondrial membrane potential (ΔmΨ), led to an increase in ΔmΨ measured by FFC. Bioenergetic studies using a Seahorse XFp metabolic analyser indicated that palmitate increased both basal oxygen consumption rate (OCR) and maximal respiration. This was coupled with a decrease in extracellular acidification rate (ECAR), suggesting reduced glycolysis. Interestingly uptake of a fluorescent glucose analogue, 2-NBDG, demonstrated that FA supply also drove an increase in glucose uptake.
Conclusion(s): The import of FA into mitochondria led to increased ΔmΨ, OCR and glucose uptake. However, ECAR was reduced, indicative of a rewiring of glucose metabolism under lipidaemic stress. Together these data suggest that FA accumulation in platelets leads to metabolic reprogramming.
To cite this abstract in AMA style:Hindle M, Naseem K. The uptake and utilisation of fatty acids by platelets. [abstract]. https://abstracts.isth.org/abstract/the-uptake-and-utilisation-of-fatty-acids-by-platelets/. Accessed September 29, 2023.
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