A high omega-3 fatty acid diet has different effects on early and late stage myeloid progenitors

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.