title: The brighter (and evolutionarily older) face of the metabolic syndrome: evidence from Trypanosoma cruzi infection in CD-1 mice.
abstract: 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.
authors.affiliation: Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY.|Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.|James J Peters VA Medical Center, Mount Sinai Medical Center Health System, Bronx, NY.|Charles University, Prague, Czech Republic.
authors.forename: Wunnie
authors.initials: W
authors.lastname: Brima
authors.affiliation: Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Eden
authors.affiliation: Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY.
authors.forename: Syed Faizan
authors.initials: SF
authors.lastname: Mehdi
authors.affiliation: Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY.
authors.forename: Michelle
authors.initials: M
authors.lastname: Bravo
authors.affiliation: Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY.
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Wiese
authors.affiliation: Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY.
authors.forename: Joanna
authors.initials: J
authors.lastname: Stein
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Almonte
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Irwin
authors.initials: I
authors.lastname: Kurland
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Pessin
authors.affiliation: Charles University, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Zima
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Tanowitz
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiss
authors.affiliation: Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY.|Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.|Hofstra North Shore-LIJ School of Medicine, North Shore-Long Island Jewish Health System, Hempstead, NY.
authors.forename: Jesse
authors.initials: J
authors.lastname: Roth
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Fnu
authors.initials: F
authors.lastname: Nagajyothi
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D014355:Chagas Disease / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D052816:Foreskin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D006352:Heart Ventricles / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D020738:Leptin / Q000097:blood / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000209:etiology / Q000276:immunology* / Q000469:parasitology; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D008815:Mice, Inbred Strains; D018448:Models, Immunological; D009765:Obesity / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D011897:Random Allocation; D016019:Survival Analysis; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity
chemical_list: D016207:Cytokines; D007004:Hypoglycemic Agents; D020738:Leptin; D008687:Metformin
keywords: Trypanosoma cruzi; high-fat diet; infectious disease; metabolic syndrome; metformin; mortality