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

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.