Polyunsaturated fatty acids alter the formation of lipid droplets and eicosanoid production in Leishmania promastigotes.

Abstract

The knowledge about eicosanoid metabolism and lipid droplet (LD) formation in the Leishmania is very limited and new approaches are needed to identify which bioactive molecules are produced of them. Herein, we compared LDs and eicosanoids biogenesis in distinct Leishmania species which are etiologic agents of different clinical forms of leishmaniasis. For this, promastigotes of Leishmania amazonensis, L. braziliensis and L. infantum were stimulated with polyunsaturated fatty acids (PUFA) and LD and eicosanoid production was evaluated. We also compared mutations in structural models of human-like cyclooxygenase-2 (GP63) and prostaglandin F synthase (PGFS) proteins, as well as the levels of these enzymes in parasite cell extracts. PUFAs modulate the LD formation in L. braziliensis and L. infantum. Leishmania spp with equivalent tissue tropism had same protein mutations in GP63 and PGFS. No differences in GP63 production were observed among Leishmania spp, however PGFS production increased during the parasite differentiation. Stimulation with arachidonic acid resulted in elevated production of hydroxyeicosatetraenoic acids compared to prostaglandins. Our data suggest LD formation and eicosanoid production are distinctly modulated by PUFAS dependent of Leishmania species. In addition, eicosanoid-enzyme mutations are more similar between Leishmania species with same host tropism.