{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:40:34Z","timestamp":1791895234574,"version":"4.3.4"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,7,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Inhibitors of the sodium\u2010glucose linked transporter 2 improve cardiovascular outcomes in patients with or without type 2 diabetes mellitus, but the effects on cardiac energetics and mitochondrial function are unknown. We assessed the effects of sodium\u2010glucose linked transporter 2 inhibition on mitochondrial function, high\u2010energy phosphates, and genes encoding mitochondrial proteins in hearts of mice with and without diet\u2010induced diabetic cardiomyopathy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Mice fed a control diet or a high\u2010fat, high\u2010sucrose diet received ertugliflozin mixed with the diet (0.5\u00a0mg\/g of diet) for 4\u00a0months. Isolated mitochondria were assessed for functional capacity. High\u2010energy phosphates were assessed by\n              <jats:sup>31<\/jats:sup>\n              P nuclear magnetic resonance spectroscopy concurrently with contractile performance in isolated beating hearts. The high\u2010fat, high\u2010sucrose diet caused myocardial hypertrophy, diastolic dysfunction, mitochondrial dysfunction, and impaired energetic response, all of which were prevented by ertugliflozin. With both diets, ertugliflozin caused supernormalization of contractile reserve, as measured by rate\u00d7pressure product at high work demand. Likewise, the myocardial gene sets most enriched by ertugliflozin were for oxidative phosphorylation and fatty acid metabolism, both of which were enriched independent of diet.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Ertugliflozin not only prevented high\u2010fat, high\u2010sucrose\u2013induced pathological cardiac remodeling, but improved contractile reserve and induced the expression of oxidative phosphorylation and fatty acid metabolism gene sets independent of diabetic status. These effects of sodium\u2010glucose linked transporter 2 inhibition on cardiac energetics and metabolism may contribute to improved structure and function in cardiac diseases associated with mitochondrial dysfunction, such as heart failure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.019995","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T09:04:10Z","timestamp":1624611850000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["Effects of Sodium\u2010Glucose Linked Transporter 2 Inhibition With Ertugliflozin on Mitochondrial Function, Energetics, and Metabolic Gene Expression in the Presence and Absence of Diabetes Mellitus in Mice"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9274-5314","authenticated-orcid":false,"given":"Dominique","family":"Croteau","sequence":"first","affiliation":[{"name":"Cardiovascular Medicine Section and Myocardial Biology Unit Boston University School of Medicine Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Luptak","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Section and Myocardial Biology Unit Boston University School of Medicine Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4285-7454","authenticated-orcid":false,"given":"Jordan M.","family":"Chambers","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Section and Myocardial Biology Unit Boston University School of Medicine Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ion","family":"Hobai","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Section and Myocardial Biology Unit Boston University School of Medicine Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Panagia","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Section and Myocardial Biology Unit Boston University School of Medicine Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Section and Myocardial Biology Unit Boston University School of Medicine Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Siwik","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Section and Myocardial Biology Unit Boston University School of Medicine Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuzhong","family":"Qin","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Section and Myocardial Biology Unit Boston University School of Medicine Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0576-9420","authenticated-orcid":false,"given":"Wilson S.","family":"Colucci","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Section and Myocardial Biology Unit Boston University School of Medicine Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2014.06.013"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.114.001597"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.002026"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.067801"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002555"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.069518"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2004967"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911303"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022190"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2020.02.004"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2018.07.006"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.01.056"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2017.07.003"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2018.01.017"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2018.7707"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm200049r"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00084.2014"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.534594"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm369"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.07.018"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-17-0457"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.235069"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-019-0816-2"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-018-0790-0"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehl526"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0991"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-016-0489-z"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165807"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.115.003643"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.23.9.1316"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.315913"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001469"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-016-0473-7"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.06.009"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.268128"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315483"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2009"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.123130"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18160-x"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-4134-x"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4509-7"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaa323"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12103-x"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.040551"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)92956-X"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.120.019995","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:15:09Z","timestamp":1715598909000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.120.019995"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,6]]},"references-count":51,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2021,7,6]]}},"alternative-id":["10.1161\/JAHA.120.019995"],"URL":"https:\/\/doi.org\/10.1161\/jaha.120.019995","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,6]]},"assertion":[{"value":"2020-12-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e019995"}}