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Recently, animal and human studies have suggested that inhibition of mTORC signaling can alleviate or prevent the development of cardiomyopathy. In view of this, we used a murine model of type 2 diabetes (T2D), BKS\u2010<jats:italic>Lepr<jats:sup>db<\/jats:sup><\/jats:italic>, to determine whether RAPA treatment can mitigate the development of T2D\u2010induced cardiomyopathy in adult mice. Female BKS\u2010<jats:italic>Lepr<jats:sup>db<\/jats:sup><\/jats:italic> mice fed diet supplemented with RAPA from 11 to 27 weeks of age showed reduced weight gain and significant reductions of fat and lean mass compared with untreated mice. No differences in plasma glucose or insulin levels were observed between groups; however, RAPA\u2010treated mice were more insulin sensitive (<jats:italic>P<\/jats:italic> &lt; 0.01) than untreated mice. Urine albumin\/creatinine ratio was lower in RAPA\u2010treated mice, suggesting reduced diabetic nephropathy and improved kidney function. Echocardiography showed significantly reduced left ventricular wall thickness in mice treated with RAPA compared with untreated mice (<jats:italic>P<\/jats:italic> = 0.02) that was consistent with reduced heart weight\/tibia length ratios, reduced myocyte size and cardiac fibrosis measured by histomorphology, and reduced mRNA expression of <jats:italic>Col1a1<\/jats:italic>, a marker for cardiomyopathy. Our results suggest that inhibition of mTORC signaling is a plausible strategy for ameliorating complications of obesity and T2D, including cardiomyopathy.<\/jats:p>","DOI":"10.1111\/nyas.13557","type":"journal-article","created":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T22:15:02Z","timestamp":1517264102000},"page":"106-117","source":"Crossref","is-referenced-by-count":20,"title":["Cardioprotective effects of dietary rapamycin on adult female C57BLKS\/J\u2010<i>Lepr<sup>db<\/sup><\/i> mice"],"prefix":"10.1111","volume":"1418","author":[{"given":"Peter C.","family":"Reifsnyder","sequence":"first","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Ryzhov","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Maine Medical Center Research Institute  Scarborough Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Flurkey","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rea P.","family":"Anunciado\u2010Koza","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Maine Medical Center Research Institute  Scarborough Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Mills","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Maine Medical Center Research Institute  Scarborough Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Harrison","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Koza","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Maine Medical Center Research Institute  Scarborough Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08221"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01255"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1381406"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/426620a"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00832.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.08215FP"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2009.00427.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1324"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44771"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016050519"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/db16-0356"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.12.010"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.235473"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.03.103"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12097"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-011-0834-3"},{"key":"e_1_2_7_18_1","first-page":"1711","article-title":"Risk of metabolic complications in patients with solid tumors treated with mTOR inhibitors: meta\u2010analysis","volume":"36","author":"Lew S.","year":"2016","journal-title":"Anticancer Res"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M100392-JLR200"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2475-7"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1215135"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.003638"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201303183"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-015-0486-5"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/4619720"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0106"},{"key":"e_1_2_7_27_1","first-page":"114","article-title":"Rapamycin modulates markers of mitochondrial biogenesis and fatty acid oxidation in the adipose tissue of db\/db mice","volume":"1","author":"Deepa S.S.","year":"2013","journal-title":"J. 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