TY - JOUR
T1 - Adipocyte-released adipomes in Chagas cardiomyopathy
T2 - Impact on cardiac metabolic and immune regulation
AU - Thangavel, Hariprasad
AU - Dhanyalayam, Dhanya
AU - Kim, Michelle
AU - Lizardo, Kezia
AU - Sidrat, Tabinda
AU - Lopez, John Gomezcoello
AU - Wang, Xiang
AU - Bansal, Shivani
AU - Nagajyothi, Jyothi F.
N1 - Publisher Copyright: © 2024 The Author(s)
PY - 2024/5/17
Y1 - 2024/5/17
N2 - 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.
AB - 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.
KW - Biology experimental methods
KW - Cell biology
KW - Disease
KW - Microbiology parasite
UR - http://www.scopus.com/inward/record.url?scp=85190423694&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2024.109672
DO - 10.1016/j.isci.2024.109672
M3 - Article
SN - 2589-0042
VL - 27
JO - iScience
JF - iScience
IS - 5
M1 - 109672
ER -