{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:36:15Z","timestamp":1791920175590,"version":"4.3.4"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Cardiac consequences of obesity include inflammation, hypertrophy, and compromised energy metabolism. Glucagon-like peptide-1 is an incretin hormone capable of cytoprotective actions that reduces inflammation and endoplasmic reticulum stress in other tissues. Here we examine the cardiac effects of the glucagon-like peptide-1 analog liraglutide in a model of obesity, independent of changes in body weight.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              C57Bl6 mice were placed on a 45% high-fat diet (HFD) or a regular chow diet. Mice on HFD developed 46\u00b12% and 60\u00b12% greater body weight relative to regular chow diet\u2013fed mice at 16 and 32 weeks, respectively (both\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001), manifesting impaired glucose tolerance, insulin resistance, and cardiac ceramide accumulation by 16 weeks. One-week treatment with liraglutide (30 \u00b5g\/kg twice daily) did not reduce body weight, but reversed insulin resistance, cardiac tumor necrosis factor-\u03b1 expression, nuclear factor kappa B translocation, obesity-induced perturbations in cardiac endothelial nitric oxide synthase, connexin-43, and markers of hypertrophy and fibrosis, in comparison with placebo-treated HFD controls. Liraglutide improved the cardiac endoplasmic reticulum stress response and also improved cardiac function in animals on HFD by an AMP-activated protein kinase\u2013dependent mechanism. Supporting a direct mechanism of action, liraglutide (100 nmol\/L) prevented palmitate-induced lipotoxicity in isolated mouse cardiomyocytes and primary human coronary smooth muscle cells and prevented adhesion of human monocytes to tumor necrosis factor-\u03b1\u2013activated human endothelial cells in vitro.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Weight-neutral treatment with a glucagon-like peptide-1 analog activates several cardioprotective pathways, prevents HFD-induced insulin resistance and inflammation, reduces monocyte vascular adhesion, and improves cardiac function in vivo by activating AMP-activated protein kinase. These data support a role for glucagon-like peptide-1 analogs in limiting the cardiovascular risks of obesity.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.112.091215","type":"journal-article","created":{"date-parts":[[2012,11,28]],"date-time":"2012-11-28T04:47:19Z","timestamp":1354078039000},"page":"74-85","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":241,"title":["A Glucagon-Like Peptide-1 Analog Reverses the Molecular Pathology and Cardiac Dysfunction of a Mouse Model of Obesity"],"prefix":"10.1161","volume":"127","author":[{"given":"Mohammad Hossein","family":"Noyan-Ashraf","sequence":"first","affiliation":[{"name":"From the Toronto General Research Institute, Toronto, Canada (M.H.N.-A., E.A.S., I.S., J.W., R.-K.L., A.V., F.B., M.H.); Hospital for Sick Children, Toronto, Canada (I.M., L.A.R.); Samuel Lunenfeld Research Institute, Toronto Canada (D.J.D.); Heart &amp; Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada (D.J.D., M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Akihiko","family":"Shikatani","sequence":"additional","affiliation":[{"name":"From the Toronto General Research Institute, Toronto, Canada (M.H.N.-A., E.A.S., I.S., J.W., R.-K.L., A.V., F.B., M.H.); Hospital for Sick Children, Toronto, Canada (I.M., L.A.R.); Samuel Lunenfeld Research Institute, Toronto Canada (D.J.D.); Heart &amp; Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada (D.J.D., M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irmgard","family":"Schuiki","sequence":"additional","affiliation":[{"name":"From the Toronto General Research Institute, Toronto, Canada (M.H.N.-A., E.A.S., I.S., J.W., R.-K.L., A.V., F.B., M.H.); Hospital for Sick Children, Toronto, Canada (I.M., L.A.R.); Samuel Lunenfeld Research Institute, Toronto Canada (D.J.D.); Heart &amp; Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada (D.J.D., M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Mukovozov","sequence":"additional","affiliation":[{"name":"From the Toronto General Research Institute, Toronto, Canada (M.H.N.-A., E.A.S., I.S., J.W., R.-K.L., A.V., F.B., M.H.); Hospital for Sick Children, Toronto, Canada (I.M., L.A.R.); Samuel Lunenfeld Research Institute, Toronto Canada (D.J.D.); Heart &amp; Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada (D.J.D., M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Toronto General Research Institute, Toronto, Canada (M.H.N.-A., E.A.S., I.S., J.W., R.-K.L., A.V., F.B., M.H.); Hospital for Sick Children, Toronto, Canada (I.M., L.A.R.); Samuel Lunenfeld Research Institute, Toronto Canada (D.J.D.); Heart &amp; Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada (D.J.D., M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren-Ke","family":"Li","sequence":"additional","affiliation":[{"name":"From the Toronto General Research Institute, Toronto, Canada (M.H.N.-A., E.A.S., I.S., J.W., R.-K.L., A.V., F.B., M.H.); Hospital for Sick Children, Toronto, Canada (I.M., L.A.R.); Samuel Lunenfeld Research Institute, Toronto Canada (D.J.D.); Heart &amp; Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada (D.J.D., M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Volchuk","sequence":"additional","affiliation":[{"name":"From the Toronto General Research Institute, Toronto, Canada (M.H.N.-A., E.A.S., I.S., J.W., R.-K.L., A.V., F.B., M.H.); Hospital for Sick Children, Toronto, Canada (I.M., L.A.R.); Samuel Lunenfeld Research Institute, Toronto Canada (D.J.D.); Heart &amp; Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada (D.J.D., M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa Annette","family":"Robinson","sequence":"additional","affiliation":[{"name":"From the Toronto General Research Institute, Toronto, Canada (M.H.N.-A., E.A.S., I.S., J.W., R.-K.L., A.V., F.B., M.H.); Hospital for Sick Children, Toronto, Canada (I.M., L.A.R.); Samuel Lunenfeld Research Institute, Toronto Canada (D.J.D.); Heart &amp; Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada (D.J.D., M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filio","family":"Billia","sequence":"additional","affiliation":[{"name":"From the Toronto General Research Institute, Toronto, Canada (M.H.N.-A., E.A.S., I.S., J.W., R.-K.L., A.V., F.B., M.H.); Hospital for Sick Children, Toronto, Canada (I.M., L.A.R.); Samuel Lunenfeld Research Institute, Toronto Canada (D.J.D.); Heart &amp; Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada (D.J.D., M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Drucker","sequence":"additional","affiliation":[{"name":"From the Toronto General Research Institute, Toronto, Canada (M.H.N.-A., E.A.S., I.S., J.W., R.-K.L., A.V., F.B., M.H.); Hospital for Sick Children, Toronto, Canada (I.M., L.A.R.); Samuel Lunenfeld Research Institute, Toronto Canada (D.J.D.); Heart &amp; Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada (D.J.D., M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansoor","family":"Husain","sequence":"additional","affiliation":[{"name":"From the Toronto General Research Institute, Toronto, Canada (M.H.N.-A., E.A.S., I.S., J.W., R.-K.L., A.V., F.B., M.H.); Hospital for Sick Children, Toronto, Canada (I.M., L.A.R.); Samuel Lunenfeld Research Institute, Toronto Canada (D.J.D.); Heart &amp; Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada (D.J.D., M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1148032"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2007"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101322"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1361"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.034"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2007.608"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7678183"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/39335"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.12.048"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.10.023"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq274"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.01.004"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1694"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0529-11.2011"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.10.001"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2009.03522.x"},{"key":"e_1_3_1_18_2","unstructured":"Novo-Nordisk. 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