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The role of fat on cardiomyopathy outcome in mouse models of chronic Trypanosoma cruzi infection

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Abstract

The underlying pathogenic mechanisms of cardiomyopathy in Chagas disease are still unsolved. In order to better clarify the role of fat on the evolution of cardiomyopathy, the present study employed three murine models of chronic Trypanosoma cruzi infection: (1) aP2-RIDα/β transgenic mice (RID mice; an adipose tissue model which express a gain-of-function potent anti-inflammatory activity), (2) allograft inflammatory factor-1 knockout mice (Aif1−/−), and (3) a Swiss outbred mice. RID mice and non-transgenic mice (wild type, WT) were infected with blood trypomastigotes of Brazil strain. During the acute stage of infection, RID mice had lower parasitemia, lower heart inflammation, and a decrease in the relative distribution of parasite load from cardiac muscle tissue toward epididymal fat. Nevertheless, comparable profiles of myocardial inflammatory infiltrates and relative distribution of parasite load were observed among RID and WT at the chronic stage of infection. Aif1−/− and Aif1+/+ mice were infected with bloodstream trypomastigotes of Tulahuen strain and fed with high-fat diet (HFD) or regular diet (RD). Interestingly, Aif1+/+ HFD infected mice showed the highest mortality. Swiss mice infected with blood trypomastigotes of Berenice-78 strain on a HFD had higher levels of TNFα and more inflammation in their heart tissue than infected mice fed a RD. These various murine models implicate adipocytes in the pathogenesis of chronic Chagas disease and suggest that HFD can lead to a significant increase in the severity of parasite-induced chronic cardiac damage. Furthermore, these data implicate adipocyte TLR4-, TNFα-, and IL-1β-mediated signaling in pro-inflammatory pathways and Aif-1 gene expression in the development of chronic Chagas disease.

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  • 20 April 2020

    The authors regret that Philipp E Scherer’s name was spelt incorrectly in the author list. The name of the author is now corrected above.

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Funding

This work was supported by the Brazilian institutions Fundação de Amparo à Pesquisa e Inovação do Espírito Santo (FAPES, grant term number 565/2015), Federal University of Espírito Santo (UFES), and by a grant from the United States of America National Institute of Allergy and Infectious Diseases AI124000.

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Author notes

  1. Paul Zaki and Elisa LBC Domingues contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    Paul Zaki, Farhad M Amjad, Huan Huang, Louis M Weiss & Herbert B Tanowitz

  2. Department of Pharmacy and Nutrition, Federal University of Espírito Santo, Guararema, Alegre, ES, 29500-000, Brazil

    Elisa LBC Domingues, Maiara B Narde, Mirelle L Viana, Heberth de Paula & Fabiane M dos Santos

  3. School of Medicine, Federal University of Ouro Preto, Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil

    Karolina R Gonçalves & Maria T Bahia

  4. Department of Biological Sciences, Federal University of Ouro Preto, Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil

    Wanderson G de Lima & Maria T Bahia

  5. The Touchstone Diabetes Center, UT Southwestern Medical Center, 5323 Harry Blvd, Dallas, TX, 75390, USA

    Philipp E Sherer

  6. Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    Louis M Weiss & Herbert B Tanowitz

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  1. Paul Zaki
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Corresponding author

Correspondence to Louis M Weiss.

Ethics declarations

All animal procedures and experimental protocols concerning experiments with transgenic aP2-RID α/β mouse model and Aif-1 target inactivated mouse model were approved by the Institutional Animal Care and Use Committees (IACUC) of Albert Einstein College of Medicine (No. 20151206) and conducted in accordance with the guidelines of the National Research Council (Guide for Care and Use of Laboratory Animals: Eight Edition, Washington, DC: The National Academic Press, 2011).

All procedures or experimental protocols conducted in the Swiss mouse model were performed according to CONCEA (National Council for Control of Animal Experimentation) and behavior instructions for the use of animals in research from Brazil. The experiment with Swiss mouse model was also previously approved by the Ethics Committee on the Use of Animals of the Federal University of Espírito Santo (protocol number 43/2015).

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Zaki, P., Domingues, E.L., Amjad, F.M. et al. The role of fat on cardiomyopathy outcome in mouse models of chronic Trypanosoma cruzi infection. Parasitol Res 119, 1829–1843 (2020). https://doi.org/10.1007/s00436-020-06645-z

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