High Fat Diet Modulates Trypanosoma cruzi Infection Associated Myocarditis

Nagajyothi, Fnu; Weiss, Louis M.; Zhao, Dazhi; Koba, Wade; Jelicks, Linda A.; Cui, Min; Factor, Stephen M.; Scherer, Philipp E.; Tanowitz, Herbert B.

doi:10.1371/journal.pntd.0003118

Cited by 53 publications

(126 citation statements)

References 23 publications

Supporting

Mentioning

115

Contrasting

Order By: Relevance

“…Tissue lysates were prepared as previously described [2-5]. An aliquot of each sample (40 μg proteins) was subjected to electrophoresis on a 4-15% gradient SDS-PAGE and the proteins transferred to nitrocellulose filters for immunoblot analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Chagas disease is a major cause of mortality and morbidity in Latin America, largely due to cardiomyopathy that develops in a large segment of the infected population [1, 2]. Recent research has demonstrated that T. cruzi causes a significant infection in adipocytes and adipose tissue, resulting in changes in adipocyte physiology that affects parasitemia, tissue parasite loads and cardiac pathology [2-4]. A western-style diet that is high in fat and processed foods is becoming prevalent in Latin America, replacing the traditional dietary system, and has been accompanied by an increased incidence of diabetes and obesity in this Chagas Disease endemic region.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have demonstrated that in a murine model of acute Chagas disease, high fat diet (HFD) has a protective effect during infection, resulting in increased survival [2, 5]. In addition, in mice fed a regular diet (RD), T. cruzi infection causes significant lipolysis (60%), which may contribute to cardiac lipidopathy and high parasite loads during acute infection [2]. In contrast, HFD ameliorates the effects of infection of adipose tissue and reduces adipocyte lipolysis [2].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, in mice fed a regular diet (RD), T. cruzi infection causes significant lipolysis (60%), which may contribute to cardiac lipidopathy and high parasite loads during acute infection [2]. In contrast, HFD ameliorates the effects of infection of adipose tissue and reduces adipocyte lipolysis [2]. Infected mice fed on an HFD also have improved cardiac pathology compared to infected mice fed on a RD.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Antagonistic effect of atorvastatin on high fat diet induced survival during acute Chagas disease

Zhao

Lizardo

Cui

et al. 2016

Microbes and Infection

Self Cite

View full text Add to dashboard Cite

Chagasic cardiomyopathy, which is seen in Chagas Disease, is the most severe and life-threatening manifestation of infection by the kinetoplastid Trypanosoma cruzi. Adipose tissue and diet play a major role in maintaining lipid homeostasis and regulating cardiac pathogenesis during the development of Chagas cardiomyopathy. We have previously reported that T. cruzi has a high affinity for lipoproteins and that the invasion rate of this parasite increases in the presence of cholesterol, suggesting that drugs that inhibit cholesterol synthesis, such as statins, could affect infection and the development of Chagasic cardiomyopathy. The dual epidemic of diabetes and obesity in Latin America, the endemic regions for Chagas Disease, has led to many patients in the endemic region of infection having hyperlipidemia that is being treated with statins such as atorvastatin. The current study was performed to examine using mice fed on either regular or high fat diet the effect of atorvastatin on T. cruzi infection-induced myocarditis and to evaluate the effect of this treatment during infection on adipose tissue physiology and cardiac pathology. Atorvastatin was found to regulate lipolysis and cardiac lipidopathy during acute T. cruzi infection in mice and to enhance tissue parasite load, cardiac LDL levels, inflammation, and mortality in during acute infection. Overall, these data suggest that statins, such as atorvastatin, have deleterious effects during acute Chagas disease.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antagonistic effect of atorvastatin on high fat diet induced survival during acute Chagas disease

Zhao

Lizardo

Cui

et al. 2016

Microbes and Infection

Self Cite

View full text Add to dashboard Cite

show abstract

“…Johndrow et al [48] demonstrated that T. cruzi induces increases in intracellular low-density lipoprotein and cholesterol in murine models during the acute and chronic phases of infection by up-regulating the low-density lipoprotein receptor, and they showed similar findings in CCC-affected human heart tissue. Nagajyothi et al [49] showed that a high fat diet in mice alters the host metabolic regulation, leading to parasite sequestration in adipose tissue and a surprising protective effect of decreased mortality, lower levels of parasitemia, and less myocardial damage during acute infection.…”

Section: Nhlbi–funded Research On Chagas Diseasementioning

confidence: 99%

Opportunities and Challenges in Chronic Chagas Cardiomyopathy

Mensah

Burns

Peprah

et al. 2015

View full text Add to dashboard Cite

The brighter (and evolutionarily older) face of the metabolic syndrome: evidence from Trypanosoma cruzi infection in CD‐1 mice

Brima

Eden

Mehdi

et al. 2015

Diabetes Metabolism Res

Self Cite

View full text Add to dashboard Cite

Infection with Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, results in chronic infection that leads to cardiomyopathy with increased mortality and morbidity in endemic regions. In a companion study, our group found that a high fat diet protected mice from Trypanosoma cruzi-induced myocardial damage, and significantly reduced post-infection mortality. In the present study, the lethality of T. cruzi (Brazil strain) infection in CD-1 mice was reduced from 55% to 20% by an 8 week pre-feeding of a high fat diet (HFD) to induce obesity and the metabolic syndrome. The addition of metformin reduced mortality to 3%. It is an interesting observation as both the high fat diet and metformin, which are known to differentially attenuate host metabolism, effectively modified mortality in T. cruzi infected mice. In humans, the metabolic syndrome, as presently construed, produces immune activation and metabolic alterations that promote complications of obesity and diseases of later life, such as myocardial infarction, stroke, diabetes, Alzheimer's disease and cancer. Using an evolutionary approach, we hypothesized that for millions of years, the channeling of host resources into immune defenses starting early in life ameliorated the effects of infectious diseases, especially chronic infections, such as tuberculosis, and Chagas disease. In economically developed countries in recent times, with control of the common devastating infections, epidemic obesity, and lengthening of life span, the dwindling benefits of the immune activation in the first half of life have been overshadowed by the explosion of the syndrome's negative effects in later life.

show abstract

High Fat Diet Modulates Trypanosoma cruzi Infection Associated Myocarditis

Cited by 53 publications

References 23 publications

Antagonistic effect of atorvastatin on high fat diet induced survival during acute Chagas disease

Antagonistic effect of atorvastatin on high fat diet induced survival during acute Chagas disease

Opportunities and Challenges in Chronic Chagas Cardiomyopathy

The brighter (and evolutionarily older) face of the metabolic syndrome: evidence from Trypanosoma cruzi infection in CD‐1 mice

Contact Info

Product

Resources

About