TRYPANOSOMA CRUZI INFECTION ALTERS ADIPOCYTE HOMEOSTASIS AFFECTING THE EXPRESSION OF METABOLIC ENZYMES, PPARS AND ADIPOKINES PROMOTING AN INFLAMMATORY PHENOTYPE

FLORENCIA BELÉN GONZALEZ, MARÍA FLORENCIA PACINI, SILVINA RAQUEL VILLAR, CECILIA FARRÉ, LUCIANO DATTILIO, OSCAR BOTTASSO, GRACIELA PIWIEN PILIPUK, ANA ROSA PÉREZ

Mar del Plata

Congreso; Reunión SAIC-SAI-SAFIS. Mar del Plata 14 al 17 de noviembre 2018; 2018

Adipose tissue (AT) is a target of T. cruzi (Tc) infection, being aparasitereservoir in mice and humans. Previously, wereported that acutemurine Tc infection is linked to a severe ATloss, probably triggeredby inflammation, as well as by the parasiteitself. Here, we evaluatedhow infection affects AT homeostasis,considering adipocyte anabolic/catabolic pathways and immune-endocrinepatterns in C57BL/6mice (n= 5-6/group) . During infection, bothcatabolic and anabolicpathways are profoundly affected, since mRNAexpression of lipolytic(HSL and ATGL) and lipogenic (LPL, FAS andDGAT) enzymesmeasured by qPCR was intensely downregulated(all enzymes, Covs Tc p<0,05). Infected AT reveals apro-inflammatory profile, with increasedleucocyte infiltration (H&E) and TNF-α overexpression (Covs Tc p<0,05). Also, AT-derivedadipokines leptin and adiponectinwere downregulated (both, Co vs Tcp<0,05). Strikingly, peroxisomeproliferator-activated receptor (PPAR)-α and PPAR-γ (transcriptionfactors that have key regulatory functionsin lipid metabolismand anti-inflammation) were stronglydecreased in AT (both, Co vsTc p<0,05), while PPAR-δ tended to diminished.AT is conformednot only by adipocytes but also by stromalvascular fraction cells(SVFCs) including CD4+ and CD8+ Tlymphocytes, macrophagesand dendritic cells; which were increasedduring infection (all, Co vsTc p<0.05) as shown by flow cytometry.Adipocytes and SVFCs wereseparated by collagenase digestion and theexpression of differentimmune-metabolic factors was assessedindependently. The samepattern of expression than observed in wholeAT was detected inisolated adipocytes from Tc animals.Coincidently, SFVCs showedan inflammatory profile with TNF-α overexpression andPPARsdownregulation (all, Co vs Tc p<0.05).These results suggest thatacute Tc infection disrupts both adipocytecatabolic and anabolicmetabolism secondary to PPARs robustdownregulation, tipping thebalance towards to an adverse statuscompatible with the AT atrophyand the acquisition of an inflammatory phenotype.