Adipocyte-released adipomes in Chagas cardiomyopathy: Impact on cardiac metabolic and immune regulation

Hariprasad Thangavel, Dhanya Dhanyalayam, Michelle Kim, Kezia Lizardo, Tabinda Sidrat, John Gomezcoello Lopez, Xiang Wang, Shivani Bansal, Jyothi F. Nagajyothi

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic Trypanosoma cruzi infection leads to Chagas cardiomyopathy (CCM), with varying manifestations such as inflammatory hypertrophic cardiomyopathy, arrhythmias, and dilated cardiomyopathy. The factors responsible for the increasing risk of progression to CCM are not fully understood. Previous studies link adipocyte loss to CCM progression, but the mechanism triggering CCM pathogenesis remains unexplored. Our study uncovers that T. cruzi infection triggers adipocyte apoptosis, leading to the release of extracellular vesicles named "adipomes". We developed an innovative method to isolate intact adipomes from infected mice's adipose tissue and plasma, showing they carry unique lipid cargoes. Large and Small adipomes, particularly plasma-derived infection-associated L-adipomes (P-ILA), regulate immunometabolic signaling and induce cardiomyopathy. P-ILA treatment induces hypertrophic cardiomyopathy in wild-type mice and worsens cardiomyopathy severity in post-acute-infected mice by regulating adipogenic/lipogenic and mitochondrial functions. These findings highlight adipomes' pivotal role in promoting inflammation and impairing myocardial function during cardiac remodeling in CD.

Original languageEnglish
Article number109672
JournaliScience
Volume27
Issue number5
DOIs
StatePublished - May 17 2024

ASJC Scopus subject areas

  • General

Keywords

  • Biology experimental methods
  • Cell biology
  • Disease
  • Microbiology parasite

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