High fat diet modulates Trypanosoma cruzi infection associated myocarditis.

Fnu Nagajyothi,Linda A Jelicks,Dazhi Zhao,Wade Koba,Louis M Weiss,Philipp E Scherer,Herbert B Tanowitz,Min-Hui Cui,Stephen M Factor,Helton Da Costa Santiago

doi:10.1371/journal.pntd.0003118

Abstract

Background Trypanosoma cruzi, the causative agent of Chagas disease, has high affinity for lipoproteins and adipose tissue. Infection results in myocarditis, fat loss and alterations in lipid homeostasis. This study was aimed at analyzing the effect of high fat diet (HFD) on regulating acute T. cruzi infection-induced myocarditis and to evaluate the effect of HFD on lipid metabolism in adipose tissue and heart during acute T. cruzi infection.Methodology/Principal FindingsCD1 mice were infected with T. cruzi (Brazil strain) and fed either a regular control diet (RD) or HFD for 35 days following infection. Serum lipid profile, tissue cholesterol levels, blood parasitemia, and tissue parasite load were analyzed to evaluate the effect of diet on infection. MicroPET and MRI analysis were performed to examine the morphological and functional status of the heart during acute infection. qPCR and immunoblot analysis were carried out to analyze the effect of diet on the genes involved in the host lipid metabolism during infection. Oil red O staining of the adipose tissue demonstrated reduced lipolysis in HFD compared to RD fed mice. HFD reduced mortality, parasitemia and cardiac parasite load, but increased parasite load in adipocytes. HFD decreased lipolysis during acute infection. Both qPCR and protein analysis demonstrated alterations in lipid metabolic pathways in adipose tissue and heart in RD fed mice, which were further modulated by HFD. Both microPET and MRI analyses demonstrated changes in infected RD murine hearts which were ameliorated by HFD.Conclusion/SignificanceThese studies indicate that Chagasic cardiomyopathy is associated with a cardiac lipidpathy and that both cardiac lipotoxicity and adipose tissue play a role in the pathogenesis of Chagas disease. HFD protected mice from T. cruzi infection-induced myocardial damage most likely due to the effects of HFD on both adipogenesis and T. cruzi infection-induced cardiac lipidopathy.

Highlights

Chagas disease, caused by the parasite Trypanosoma cruzi, is classified by WHO as a neglected tropical disease and is a major cause of morbidity and mortality in Latin America [1]
We demonstrated that adipose tissue is an early target and a reservoir for T. cruzi
For the first time, the effect of diet on myocardial inflammation and damage observed during acute T. cruzi infection and provide data on the role of parasite associated low density lipoprotein (LDL)/high density lipoprotein (HDL) in the regulation of systemic lipid homeostasis in white adipose tissue (WAT) and in the heart

Summary

Introduction

Chagas disease, caused by the parasite Trypanosoma cruzi, is classified by WHO as a neglected tropical disease and is a major cause of morbidity and mortality in Latin America [1]. Acute systemic infection is often asymptomatic, but, in those that are symptomatic the disease is characterized by myocarditis and/or meningoencephalitis [1,2,3]. T. cruzi infection causes an intense systemic pro-inflammatory response in many organs including the heart. Trypanosoma cruzi, the causative agent of Chagas disease, has high affinity for lipoproteins and adipose tissue. This study was aimed at analyzing the effect of high fat diet (HFD) on regulating acute T. cruzi infection-induced myocarditis and to evaluate the effect of HFD on lipid metabolism in adipose tissue and heart during acute T. cruzi infection

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Conclusion