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

S.R. VILLAR; MARQUEZ JULIA; GRACIELA PIWIEN-PILIPUK; JUDITH TONEATTO; D´ATTILIO LUCIANO; ANA ROSA PEREZ; GONZALEZ FLORENCIA; M. FLORENCIA PACINI; BOTTASSO OSCAR

Resistencia, Chaco

Congreso; XXX Reunion Anual SAP; 2018

Sociedad Argentina de Protozoologia

MESA REDONDA INMUNOLOGIA DIsertante: Ana R. Perez(pag 25 en Libro de Resumenes)Adipose tissue is an endocrine, but also immune organ, producing a wide range of mediators, likeadipocytokines. Adipose tissue is a target of T. cruzi infection being a parasite reservoir during thechronic phase in mice and humans, but its role during the acute phase is still not well known.C57BL/6 mice infected with T. cruzi showed a fatal disease associated with a dysregulated immuneendocrineresponse characterized by deleterious synthesis of pro-inammatory cytokines, hypoglycemiaand a marked reduction in the adipose tissue. Moreover, the infection coexists with a dysregulationof leptin/hypothalamic ObR circuitry dissociated from adipose tissue loss and food intake control.The severe adipose tissue loss may be triggered by inammation, as well as caused by the parasiteitself. To determine how the infection impacts on adipose tissue we also evaluated immune-metabolicparameters in the epididymal adipose tissue. Our studies showed that during in vivo infection, bothlipolytic and lipogenic pathways are profoundly aected since the expression of lipolytic and lipogenicenzymes was intensely down-regulated. A similar pattern was observed in isolated adipocytes frominfected animals and in 3T3-L1 adipocytes infected in vitro with T. cruzi. Moreover, in vivo infectedadipose tissue reveals a pro-inammatory prole, with increased leucocyte inltration accompaniedby TNF- and IL-6 overexpression and leptin and adiponectin downregulation. The nuclear factorPPAR- is a key factor involved in adipogenesis and metabolism and has been also implicated inthe down-regulation of inammation. During in vivo T. cruzi infection, PPAR- expression is stronglydiminished in adipocytes. Attempts to favor PPAR--mediated actions in the adipose tissue of infectedanimals by using agonists failed, indicating that inammation or parasite-derived factors are stronglyinvolved in PPAR- inhibition. Here we report that experimental acute T. cruzi infection disruptsadipocyte catabolic and anabolic metabolism secondary to PPAR- robust downregulation, tippingthe balance towards to an adverse status compatible with the adipose tissue atrophy and the acquisitionof an inammatory phenotype.