EFFECTS OF PPAR-ã AGONISTS ON ADIPOSE TISSUE, IMMUNE AND METABOLIC PARAMETERS DURING ACUTE Trypanosoma cruzi INFECTION

FLORENCIA B. GONZáLEZ; JULIA S. MáRQUEZ; EDUARDO A ROGGERO; SILVINA R. VILLAR, OSCAR BOTTASSO, ANA R. PéREZ.

Mar del Plata

Congreso; X Congreso de protozoología y enfermedades parasitarias; 2014

Sociedad de Protozoologia

Adipose tissue (TA) influences energy homeostasis and inflammation and at the same time can act as a T. cruzi (Tc) reservoir. We recently showed that mice infected with Tc displayed an exacerbated pro-inflammatory milieu associated with  metabolic abnormalities like manifest lipolysis, hypoglycemia, hypoleptinemia, reduced body weight and food intake which may play a role in lethality. PPAR-ã is a ligand-activated nuclear factor mainly expressed in adipocytes and is involved in the modulation of energetic metabolism and down regulation of inflammation. Thus, we wished to ascertain whether therapeutic administration of endogenous (15dPGJ2; PGJ) or synthetic PPAR-ã agonists (Rosiglitazone, RGZ) improved metabolic and AT inflammatory parameters and influenced the course of T. cruzi infection. Mice were treated during the first 10 days post-infection (dpi) with PGJ (1 mg/kg) or RGZ (10 & 20 mg/kg) and sacrificed after 17 dpi or maintained alive to record survival. In infected mice both agonists failed to induce major changes in survival, body weight loss, food intake, glycemia and systemic leptin levels, probably related with a downregulation of PPAR-ã  in AT during infection. On the other hand, both drugs slightly reduced lipolysis, AT inflammation and macrophage phagocytosis. AT-derived immune cells from infected animals showed an increase in CD8+ T cells, CD11b+ and CD11c+ cells, with a diminution of CD4+Foxp3+ Treg cells. In addition, RZG treated Tc animals displayed a higher proportion of AT CD11b+ and CD11b+CD11c+  cells compared to untreated Tc mice (p<0,05). Even though both agonists increased parasite load, only minor changes were found in heart tissue inflammation. Collectively, AT abnormalities and immune changes seen during acute Tc infection were slightly improved by PPAR-ã agonists, while they failed to modify the outcome of infection. Downregulation of PPAR-ã by pro-inflammatory cytokines might be responsible for the unresponsiveness of PPAR-ã agonists.