BACKGROUND: 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 (HFD) protected mice from T. cruzi-induced myocardial damage and significantly reduced post-infection mortality during acute T. cruzi infection. METHODS: In the present study metabolic syndrome was induced prior to T. cruzi infection by feeding a high fat diet. Also, mice were treated with anti-diabetic drug metformin. RESULTS: 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 an HFD to induce obesity and metabolic syndrome. The addition of metformin reduced mortality to 3%. CONCLUSIONS: It is an interesting observation that both the high fat diet and the 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 defences 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 lifespan, 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.

• Klíčová slova
• Trypanosoma cruzi, high-fat diet, infectious disease, metabolic syndrome, metformin, mortality,
• MeSH
• adipozita účinky léků   MeSH
• analýza přežití MeSH
• bílá tuková tkáň účinky léků   imunologie   metabolismus   parazitologie   MeSH
• buněčné linie MeSH
• Chagasova nemoc krev   imunologie   metabolismus   parazitologie   MeSH
• cytokiny krev   metabolismus   MeSH
• energetický metabolismus účinky léků   MeSH
• hypoglykemika farmakologie   terapeutické užití   MeSH
• inbrední kmeny myší MeSH
• leptin krev   metabolismus   MeSH
• lidé MeSH
• metabolický syndrom farmakoterapie   etiologie   imunologie   parazitologie   MeSH
• metformin farmakologie   terapeutické užití   MeSH
• modely imunologické * MeSH
• náhodné rozdělení MeSH
• obezita krev   imunologie   metabolismus   patofyziologie   MeSH
• předkožka účinky léků   imunologie   metabolismus   parazitologie   MeSH
• srdeční komory účinky léků   imunologie   metabolismus   parazitologie   MeSH
• Trypanosoma cruzi účinky léků   imunologie   izolace a purifikace   patogenita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• srovnávací studie MeSH
• Názvy látek
• cytokiny MeSH
• hypoglykemika MeSH
• leptin MeSH
• metformin MeSH