Abstract
Adipose tissue is a target of Trypanosoma cruzi infection being a parasite reservoir during the chronic phase in mice and humans. Previously, we reported that acute Trypanosoma cruzi infection in mice is linked to a severe adipose tissue loss, probably triggered by inflammation, as well as by the parasite itself. Here, we evaluated how infection affects adipose tissue homeostasis, considering adipocyte anabolic and catabolic pathways, the immune–endocrine pattern and the possible repercussion upon adipogenesis. During in vivo infection, both lipolytic and lipogenic pathways are profoundly affected, since the expression of lipolytic enzymes and lipogenic enzymes was intensely downregulated. A similar pattern was observed in isolated adipocytes from infected animals and in 3T3-L1 adipocytes infected in vitro with Trypanosoma cruzi. Moreover, 3T3-L1 adipocytes exposed to plasmas derived from infected animals also tend to downregulate lipolytic enzyme expression which was less evident regarding lipogenic enzymes. Moreover, in vivo-infected adipose tissue reveals a pro-inflammatory profile, with increased leucocyte infiltration accompanied by TNF and IL-6 overexpression, and adiponectin downregulation. Strikingly, the nuclear factor PPAR-γ is strongly decreased in adipocytes during in vivo infection. Attempts to favor PPAR-γ-mediated actions in the adipose tissue of infected animals using agonists failed, indicating that inflammation or parasite-derived factors are strongly involved in PPAR-γ inhibition. Here, we report that experimental acute Trypanosoma cruzi infection disrupts both adipocyte catabolic and anabolic metabolism secondary to PPAR-γ robust downregulation, tipping the balance towards to an adverse status compatible with the adipose tissue atrophy and the acquisition of an inflammatory phenotype.
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Acknowledgements
ARP, GPP, JT, LD, OAB and SRV are members of The National Council Research (CONICET). FBG thanks CONICET for a fellowship. JM thanks CIN (National Interuniversity Council) for a fellowship. This work was supported by grants from the Secretary of Sciences and Technology of National University of Rosario (SCYTUNR, 1MED-348 and 1MED-372), National Agency for Scientific and Technological Promotion (ANPCYT, PICT 2013-1892) and PIP-CONICET 0614. The authors thank Wiener Lab. Foundation for their help in supplying some laboratory reagents. We thank Farré Cecilia, Esdras da Silva Oliveira Barbosa and Cabral Nicolás by their technical assistance.
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The latest National Institute of Health guide for the care and use of laboratory was followed. The study was approved by the Institutional Animal Care and Use Committee of the School of Medicine of National University of Rosario by resolution no. 4977/2013.
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González, F.B., Villar, S.R., Toneatto, J. et al. Immune response triggered by Trypanosoma cruzi infection strikes adipose tissue homeostasis altering lipid storage, enzyme profile and adipokine expression. Med Microbiol Immunol 208, 651–666 (2019). https://doi.org/10.1007/s00430-018-0572-z
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DOI: https://doi.org/10.1007/s00430-018-0572-z