Abstract 12411: Fatty Acid Saturation Status in Murine High Fat Diets Modulates Platelet Reactivity

Abstract

Introduction: We have recently shown that membrane fatty acids are key modulators of megakaryocyte differentiation and platelet formation. In obesity, patients have an altered plasma lipid composition, which coincides with enhanced platelet responsiveness to activation. However, the mechanism underlying this platelet phenotype remains unknown. Hypothesis: We hypothesized that the obese plasma lipidome alters the composition of the megakaryocyte membrane, which ultimately leads to the generation of hyper-reactive platelets. Aim: To investigate the impact of high fat diets with different fatty acid compositions on megakaryocyte development and platelet reactivity. Results: Mice were fed chow or high fat diets enriched in either saturated fatty acids (50% SFAs) or polyunsaturated fatty acids (50% PUFAs, omega-6-enriched). Neither high fat diet resulted in changes in megakaryocyte numbers, but both caused a significant increase in the size of bone marrow megakaryocytes, suggesting diet-derived lipid uptake into megakaryocytes. When examining platelet reactivity, we found that mice fed the SFA-enriched high fat diet exhibited increased expression of the active form of integrin αIIbβ3 (JON/A) in resting platelets and that both JON/A and P-selectin expression were significantly decreased after platelets were stimulated with ADP and the thromboxane A 2 analogue U46619. In contrast, platelets from mice fed the PUFA omega-6-enriched high fat diet had no differences in platelet reactivity compared to mice fed normal chow. Conclusions: Our data reveal that dietary fatty acid saturation status affects platelet reactivity, consistent with previous human studies showing variability in platelet reactivity in obese individuals. Further explorations will elucidate if plasma and/or platelet lipid content may be an indicator of risk for thrombosis or cardiovascular disease.