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 5x10 4 and 10 3 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.

中文翻译：

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脂肪组织调节鼠恰加斯病心肌病的发病机制和严重程度。

由寄生虫克氏锥虫引起的慢性恰加斯氏心肌病（CCC）在拉丁美洲是一种威胁生命的疾病，目前尚无有效的药物或疫苗。CCC的发病机制是复杂和多因素的。以前，我们证明了感染克氏锥虫的小鼠会丢失大量的脂肪组织，这与CCC的进展有关。在此基础上，进行了一项调查，利用FAT-ATTAC鼠模型（允许调节脂肪量）在急性和慢性克鲁氏杆菌感染期间进行研究，以了解脂肪细胞损失在调节心脏寄生虫负荷，寄生虫持久性方面的后果。 ，炎症，线粒体应激，内质网应激，生存，CCC进展和CCC严重程度。小鼠腹膜内感染5x10 4和10 3的锥虫病，分别产生急性和慢性Chagas模型。通过在15DPI（急性感染）和65DPI（不确定感染）开始的AP21087处理10天，在未感染和感染的小鼠中进行脂肪细胞的消融。在急性感染期间，心脏超声成像，组织学和生化分析表明，消融脂肪会增加心脏寄生虫负荷，心脏病理学和右心室扩张并降低生存率。在慢性不确定感染期间，脂肪细胞的消融会增加心脏病理，并引起双心室扩张。这些数据表明功能失调的脂肪组织不仅会影响心脏代谢，还会影响炎症状态，