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Trypanosoma cruzi down-regulates adiponectin expression in mouse adipocytes via the NFAT signaling pathway
Miguel H Santamaría1, Luisa Delgado Ríos1, Ricardo S Corral2
1Laboratorio de Biología Experimental, Centro de Estudios Metabólicos, Santander, Cantabria, Spain.
Abstract:
Upon infection by Trypanosoma cruzi, adipocytes adopt a clearly defined inflammatory phenotype with concomitant down-regulation of adiponectin expression, which influences the pathogenesis of Chagas heart disease. Herein, we examined how T. cruzi interferes with transcriptional regulation of adiponectin production in mouse adipocytes. The invading pathogen activates the Ca2+/calcineurin/NFATc4 signaling pathway in 3T3-L1 cells. Parasite-induced early activation of NFATc4 is involved in repressing adiponectin expression through recognition of the specific response element located at (-363 to -344) of the gene promoter. Nuclear import of dephosphorylated NFATc4 and decreased adiponectin levels were further demonstrated in white adipose tissue from acutely infected mice. Our current findings point to better clarify the complex role of adipose tissue in the modulation of inflammatory mechanisms operative during T. cruzi infection.
Insights
Trypanosoma cruzi infection triggers inflammation in fat cells, reducing adiponectin. This pathway, involving NFATc4 signaling, contributes to Chagas heart disease pathogenesis.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- Adipocytes exhibit an inflammatory phenotype during Trypanosoma cruzi infection.
- Adiponectin expression is downregulated, impacting Chagas heart disease.
- The role of adipose tissue in T. cruzi infection pathogenesis requires further clarification.
Purpose of the Study:
- To investigate how T. cruzi interferes with adiponectin gene transcriptional regulation in mouse adipocytes.
- To elucidate the signaling pathways involved in parasite-induced adiponectin downregulation.
Main Methods:
- Utilized 3T3-L1 cells and white adipose tissue from infected mice.
- Examined the Ca2+/calcineurin/NFATc4 signaling pathway.
- Analyzed the specific response element in the adiponectin gene promoter.
Main Results:
- T. cruzi infection activates the Ca2+/calcineurin/NFATc4 pathway in adipocytes.
- NFATc4 activation represses adiponectin expression by binding to a specific promoter region.
- Decreased adiponectin levels and NFATc4 nuclear import were observed in infected mouse adipose tissue.
Conclusions:
- NFATc4 signaling is a key mechanism by which T. cruzi downregulates adiponectin.
- Adipose tissue plays a complex role in modulating inflammatory responses during T. cruzi infection.
- Findings enhance understanding of Chagas heart disease pathogenesis.
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