{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T13:33:49Z","timestamp":1767706429720,"version":"3.37.3"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,6]],"date-time":"2015-03-06T00:00:00Z","timestamp":1425600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung and Blood Institute- NIH","doi-asserted-by":"crossref","award":["112099"],"award-info":[{"award-number":["112099"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Alan and Tatyana Forman Family"},{"name":"The Feinstein Institute for Medical Research"},{"name":"The Russell Berrie Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Infection with <jats:italic>Trypanosoma cruzi<\/jats:italic>, 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\u2010fat diet (HFD) protected mice from <jats:italic>T<\/jats:italic>.\u2009<jats:italic>cruzi<\/jats:italic>\u2010induced myocardial damage and significantly reduced post\u2010infection mortality during acute <jats:italic>T<\/jats:italic>.\u2009<jats:italic>cruzi<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the present study metabolic syndrome was induced prior to <jats:italic>T. cruzi<\/jats:italic> infection by feeding a high fat diet. Also, mice were treated with anti\u2010diabetic drug metformin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the present study, the lethality of <jats:italic>T<\/jats:italic>.\u2009<jats:italic>cruzi<\/jats:italic> (Brazil strain) infection in CD\u20101 mice was reduced from 55% to 20% by an 8\u2010week pre\u2010feeding of an HFD to induce obesity and metabolic syndrome. The addition of metformin reduced mortality to 3%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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 <jats:italic>T<\/jats:italic>.\u2009<jats:italic>cruzi<\/jats:italic>\u2010infected 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. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dmrr.2636","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T00:53:42Z","timestamp":1421974422000},"page":"346-359","source":"Crossref","is-referenced-by-count":34,"title":["The brighter (and evolutionarily older) face of the metabolic syndrome: evidence from <i>Trypanosoma cruzi<\/i> infection in CD\u20101 mice"],"prefix":"10.1002","volume":"31","author":[{"given":"Wunnie","family":"Brima","sequence":"first","affiliation":[{"name":"Laboratory of Diabetes and Diabetes\u2010related Research, Feinstein Institute for Medical Research North Shore\u2010Long Island Jewish Health System  Manhasset NY USA"},{"name":"Department of Pathology Albert Einstein College of Medicine  Bronx NY USA"},{"name":"James J. Peters VA Medical Center Mount Sinai Medical Center Health System  Bronx NY USA"},{"name":"Charles University  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Eden","sequence":"additional","affiliation":[{"name":"Laboratory of Diabetes and Diabetes\u2010related Research, Feinstein Institute for Medical Research North Shore\u2010Long Island Jewish Health System  Manhasset NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Faizan","family":"Mehdi","sequence":"additional","affiliation":[{"name":"Laboratory of Diabetes and Diabetes\u2010related Research, Feinstein Institute for Medical Research North Shore\u2010Long Island Jewish Health System  Manhasset NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Bravo","sequence":"additional","affiliation":[{"name":"Laboratory of Diabetes and Diabetes\u2010related Research, Feinstein Institute for Medical Research North Shore\u2010Long Island Jewish Health System  Manhasset NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad M.","family":"Wiese","sequence":"additional","affiliation":[{"name":"Laboratory of Diabetes and Diabetes\u2010related Research, Feinstein Institute for Medical Research North Shore\u2010Long Island Jewish Health System  Manhasset NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Stein","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Feinstein Institute for Medical Research North Shore Long\u2010Island Jewish Health System  Manhasset NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Almonte","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine  Bronx NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dazhi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine  Bronx NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irwin","family":"Kurland","sequence":"additional","affiliation":[{"name":"Department of Medicine Albert Einstein College of Medicine  Bronx NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey E.","family":"Pessin","sequence":"additional","affiliation":[{"name":"Department of Medicine Albert Einstein College of Medicine  Bronx NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomas","family":"Zima","sequence":"additional","affiliation":[{"name":"Charles University  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert B.","family":"Tanowitz","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine  Bronx NY USA"},{"name":"Department of Medicine Albert Einstein College of Medicine  Bronx NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis M.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine  Bronx NY USA"},{"name":"Department of Medicine Albert Einstein College of Medicine  Bronx NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse","family":"Roth","sequence":"additional","affiliation":[{"name":"Laboratory of Diabetes and Diabetes\u2010related Research, Feinstein Institute for Medical Research North Shore\u2010Long Island Jewish Health System  Manhasset NY USA"},{"name":"Department of Pathology Albert Einstein College of Medicine  Bronx NY USA"},{"name":"Hofstra North Shore\u2010LIJ School of Medicine North Shore\u2010Long Island Jewish Health System  Hempstead NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fnu","family":"Nagajyothi","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine  Bronx NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,3,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2012.109"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001136"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003118"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000111245.75752.C6"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000217840.26971.b6"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.930"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.110.001909"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00115312"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-7-81"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2012.09.126"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.167.12.1297"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.1.152-159.2006"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.11.027"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-011-2790-9"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(89)90126-5"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1975.24.25"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2014.01.001"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir840"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2012.01764.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2008.331"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412802200"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2003.11.013"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830260116"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(99)00172-8"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001598"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004331"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28898"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0431rev"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1086\/656189"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.7.4075-4083.2000"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-014-3977-7"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000953"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(75)90182-8"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803563"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1316925111"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.01126.x"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-013-2979-3"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0801"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/35008121"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.4067\/S0034-98872012001100001"}],"container-title":["Diabetes\/Metabolism Research and Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fdmrr.2636","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dmrr.2636","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T14:17:05Z","timestamp":1696601825000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dmrr.2636"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,6]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1002\/dmrr.2636"],"URL":"https:\/\/doi.org\/10.1002\/dmrr.2636","archive":["Portico"],"relation":{},"ISSN":["1520-7552","1520-7560"],"issn-type":[{"type":"print","value":"1520-7552"},{"type":"electronic","value":"1520-7560"}],"subject":[],"published":{"date-parts":[[2015,3,6]]}}}