TY - JOUR
T1 - The brighter (and evolutionarily older) face of the metabolic syndrome
T2 - Evidence from Trypanosoma cruzi infection in CD-1 mice
AU - Brima, Wunnie
AU - Eden, Daniel J.
AU - Mehdi, Syed Faizan
AU - Bravo, Michelle
AU - Wiese, Mohammad M.
AU - Stein, Joanna
AU - Almonte, Vanessa
AU - Zhao, Dazhi
AU - Kurland, Irwin
AU - Pessin, Jeffrey E.
AU - Zima, Tomas
AU - Tanowitz, Herbert B.
AU - Weiss, Louis M.
AU - Roth, Jesse
AU - Nagajyothi, Fnu
N1 - Publisher Copyright:
© 2015 John Wiley & Sons, Ltd.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - High-fat diet
KW - Infectious disease
KW - Metabolic syndrome
KW - Metformin
KW - Mortality
KW - Trypanosoma cruzi
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U2 - 10.1002/dmrr.2636
DO - 10.1002/dmrr.2636
M3 - Article
C2 - 25613819
AN - SCOPUS:84928209062
SN - 1520-7552
VL - 31
SP - 346
EP - 359
JO - Diabetes/Metabolism Research and Reviews
JF - Diabetes/Metabolism Research and Reviews
IS - 4
ER -