Immune response triggered by Trypanosoma cruzi infection affects adipocyte homeostasis and adipokine axis

GONZÁLEZ B.F., VILLAR S.R., TONEATTO J., PACINI M.F., MÁRQUEZ J., D´ATTILIO L., BOTTASSO O.A., PIWIEN-PILIPUK G., PÉREZ A.R.

Resistencia, Chaco

Congreso; XXX Reunión de la Sociedad Argentina de Protozoología.; 2018

Adiposetissue is an endocrine, but also immune organ, producing a wide range ofmediators, like adipocytokines. Adipose tissue is a target of T. cruzi infection being a parasite reservoir during the chronicphase in mice and humans, but its role during the acute phase is still not wellknown.C57BL/6mice infected with T. cruzi showed a fatal disease associated with a dysregulated immuneendocrine responsecharacterized by deleterious synthesis of pro-inammatory cytokines,hypoglycemia and a marked reduction in the adipose tissue. Moreover, theinfection coexists with a dysregulation of leptin/hypothalamic ObR circuitrydissociated from adipose tissue loss and food intake control.Thesevere adipose tissue loss may be triggered by inammation, as well as caused bythe parasite itself. To determine how the infection impacts on adipose tissuewe also evaluated immune-metabolic parameters in the epididymal adipose tissue.Our studies showed that during in vivo infection, both lipolytic and lipogenic pathways are profoundly a_ectedsince the expression of lipolytic and lipogenic enzymes was intenselydown-regulated. A similar pattern was observed in isolated adipocytes from infectedanimals and in 3T3-L1 adipocytes infected in vitro with T. cruzi. Moreover, invivo infected adipose tissue reveals a pro-inammatorypro_le, with increased leucocyte in_ltration accompaniedbyTNF-a and IL-6overexpression and leptin and adiponectin downregulation. The nuclear factor PPAR- is a key factor involved in adipogenesis andmetabolism and has been also implicated in the down-regulation of inammation.During in vivo T. cruzi infection,PPAR- expression isstrongly diminished in adipocytes. Attempts to favor PPAR--mediated actions inthe adipose tissue of infected animals by using agonists failed, indicatingthat inammation or parasite-derived factors are strongly involved in PPAR- inhibition. Here we report that experimentalacute T. cruzi infectiondisrupts adipocyte catabolic and anabolic metabolism secondary to PPAR- robust downregulation, tipping the balancetowards to an adverse status compatible with the adipose tissue atrophy and theacquisition of an inammatory phenotype.