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The effects of the polyunsaturated omega-3 (n-3) and omega-6 (n-6) fatty acids (FA) on hematopoiesis are complex in that both FA forms are processed into leukotrienes, eicosanoids, and prostaglandins, which can have independent effects. These FA have antagonistic effects in that n-6 FA prostaglandins tend to be pro-proliferative and pro-inflammatory, while the effects of n-3 FA prostaglandins are the opposite. We have previously shown that diets high in n-3 FA reduce the size of the middle to later stage myeloid progenitor compartment in FVB X sv129 F(1)hybrid mice. To assay the effects of high n-3 FA diets on earlier stages of myelopoiesis, we fed C57BL/6J mice diets high in n-3 FA or levels of n-3/n-6 FA similar to western diets and assayed the effects on myelopoiesis with flow cytometry and colony forming cell assays. Results indicate an expansion of the common myeloid progenitor cell compartment in high n-3 FA diets, which does not persist into later stages where the number of progenitor cells is actually lower in high n-3 FA fed animals. Investigations in vitro with the hematopoietic stem cell line EML-clone 1 indicate that cells cultured with eicosapentaenoic acid (n-3 FA) or arachidonic acid (n-6 FA) have no differences in cell viability but that arachidonic acid more rapidly produces progenitors with low levels of the macrophage developmental marker, F4/80.

Background: Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias., Results: We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts., Conclusion: Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.