Fat tissue regulates the pathogenesis and severity of cardiomyopathy in murine chagas disease

Kezia Lizardo, Janeesh P. Ayyappan, Neelam Oswal, Louis M. Weiss, Philipp E. Scherer, Jyothi F. Nagajyothi

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Chronic Chagas cardiomyopathy (CCC) caused by a parasite Trypanosoma cruzi is a life-threatening disease in Latin America, for which there is no effective drug or vaccine. The pathogenesis of CCC is complex and multifactorial. Previously, we demonstrated T. cruzi infected mice lose a significant amount of fat tissue which correlates with progression of CCC. Based on this an investigation was undertaken during both acute and chronic T. cruzi infection utilizing the FAT-ATTAC murine model (that allows modulation of fat mass) to understand the consequences of the loss of adipocytes in the regulation of cardiac parasite load, parasite persistence, inflammation, mitochondrial stress, ER stress, survival, CCC progression and CCC severity. Mice were infected intraperitoneally with 5x104 and 103 trypomastigotes to generate acute and chronic Chagas models, respectively. Ablation of adipocytes was carried out in uninfected and infected mice by treatment with AP21087 for 10 days starting at 15DPI (acute infection) and at 65DPI (indeterminate infection). During acute infection, cardiac ultrasound imaging, histological, and biochemical analyses demonstrated that fat ablation increased cardiac parasite load, cardiac pathology and right ventricular dilation and decreased survival. During chronic indeterminate infection ablation of fat cells increased cardiac pathology and caused bi-ventricular dilation. These data demonstrate that dysfunctional adipose tissue not only affects cardiac metabolism but also the inflammatory status, morphology and physiology of the myocardium and increases the risk of progression and severity of CCC in murine Chagas disease.

Original languageEnglish (US)
Article numbere0008964
JournalPLoS neglected tropical diseases
Volume15
Issue number4
DOIs
StatePublished - Apr 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Fat tissue regulates the pathogenesis and severity of cardiomyopathy in murine chagas disease'. Together they form a unique fingerprint.

Cite this