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

Wunnie Brima, Daniel J. Eden, Syed Faizan Mehdi, Michelle Bravo, Mohammad M. Wiese, Joanna Stein, Vanessa Almonte, Dazhi Zhao, Irwin Kurland, Jeffrey E. Pessin, Tomas Zima, Herbert B. Tanowitz, Louis M. Weiss, Jesse Roth, Fnu Nagajyothi

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)346-359
Number of pages14
JournalDiabetes/Metabolism Research and Reviews
Issue number4
StatePublished - May 1 2015


  • High-fat diet
  • Infectious disease
  • Metabolic syndrome
  • Metformin
  • Mortality
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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