Functional evaluation of fatty acid binding protein 4 (FABP4) and PPAR-gamma modulation in Leishmania amazonensis

Abstract

Amastigote forms of the Leishmania genus reside in parasitophorous vacuoles of mononuclear phagocytic cells.Currently, little is known about the molecular mechanisms that control the metabolism of Leishmania in these organelles, regarding both biosynthesis of macromolecules and the metabolic control of the host cell by the parasite itself.Preliminary studies of transcriptomic analysis demonstrated that there is an increase in the levels of FABP4 (fatty acid binding protein 4) transcripts in macrophages infected with Leishmania (Leishmania) amazonensis for 48 hours.FABPs are small intracellular proteins that easily access the cell nucleus under certain physiological conditions and act as transporters of fatty acids binding transcription factors, such as peroxisome proliferator-activated receptors (eg. PPAR-alpha and gamma) and the type 4FABP, responsible for the transport of fatty acids to different cellular compartments in both macrophages and adipocytes.Based on the biological properties described for FABP4, in addition to the fact that the amastigote form depends on the metabolism of fatty acids for amino acid biosynthesis, it is reasonable to postulate that macrophagic FABP4 may play an important role in lipid homeostasis in the infected cell during the infection process.Thus, in the present study, we intend to investigate the role of FABP4 from in vitro infection assays in macrophages with reduced expression of the FABP4 gene (using interference by RNA).In addition, the involvement of PPAR-gamma in the FABP4-mediated signaling pathway will be investigated, by the evaluation of both levels of the binding protein and Leishmania amazonensis infections in PPAR-gamma-KO mice and in macrophages from PPAR-gamma-KO mice. (AU)