Our hypothesis is that polyunsaturated fatty acid (PUFA) enriched diets have a major action on megakaryocytes. The megakaryocyte is a bone marrow cell whose primary function is to synthesize platelets, and the platelet itself has little synthetic capacity. Megakaryocytes have a greater capacity for lipid metabolism and most likely determine a substantial portion of the lipid composition of platelets. For example, megakaryocytes but not platelets have been shown to synthesize cholesterol and can desaturate eicosatrienoic acid for the synthesis of arachidonic acid. Thus, megakaryocytes would be a more likely target for PUFA-enriched diets than platelets. The goals of the study are to determine the effects of omega 3 fatty acids, eicosapentaenoic and docosahexaenoic, and alpha linolenic acid, as well as the omega 6 fatty acids, linoleic and gamma linolenic acids on megakaryocytes. Guinea pigs will be fed diets enriched with these PUFA and the animals will be sacrificed at various time intervals and megakaryocytes and platelets will be isolated and subjected to lipid analysis. The effects of PUFA-modified diets on the lipid composition, desaturase activity, and the uptake and transfer of arachidonic acid and other unsaturated fatty acids will be determined. The effects of dietary manipulation of PUFA on acyltransferase and transacylase activities, which regulate the distribution of fatty acids in cellular phospholipids, will be studied. There is evidence desaturases and acyltransferases are sensitive to PUFA-modified diets. The study will detemine whether the effects of PUFA-enriched diets occur earlier in megakaryocytes and whether the effects on megakaryocytes are different or of greater magnitude than those on platelets. Alterations in lipid composition and metabolism will be correlated with the production of eicosanoids, with the effects on megakaryocyte biology, and the ability of megakaryocytes to produce structurally and functionally normal platelets. This information should define the effects of the PUFA-enriched diets on megakaryocytes in comparison to platelets. The study will test our contention that PUFA-modified diets by primarily acting on megakaryocytes influence the composition and distribution of unsaturated fatty acids in platelets and thus the availability of arachidonic acid for the production of eicosanoids. As yet, the effects of PUFA-enriched diets on megakaryocytes have not been investigated. Therefore, the study should provide important new insights into the mechanisms for PUFA-diet related platelet impairment.
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