{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T03:09:03Z","timestamp":1775272143658,"version":"3.50.1"},"reference-count":70,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2018,11,10]],"date-time":"2018-11-10T00:00:00Z","timestamp":1541808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009364","name":"Saving Tiny Hearts Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000970","name":"Stem Cells Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000970","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004079","name":"Konrad-Adenauer-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004079","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004752","name":"State Government of Victoria","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004752","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1069710"],"award-info":[{"award-number":["1069710"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Metabolism"],"published-print":{"date-parts":[[2019,2]]},"DOI":"10.1016\/j.molmet.2018.11.002","type":"journal-article","created":{"date-parts":[[2018,11,15]],"date-time":"2018-11-15T10:39:46Z","timestamp":1542278386000},"page":"102-114","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["Metformin intervention prevents cardiac dysfunction in a murine model of adult congenital heart disease"],"prefix":"10.1016","volume":"20","author":[{"given":"Julia C.","family":"Wilmanns","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raghav","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"Hon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anjana","family":"Chandran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan M.","family":"Schilling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elvira","family":"Forte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8819-7976","authenticated-orcid":false,"given":"Qizhu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gael","family":"Cagnone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preeti","family":"Bais","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivek","family":"Philip","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Coleman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"Kocalis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart K.","family":"Archer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3318-5406","authenticated-orcid":false,"given":"James T.","family":"Pearson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirana","family":"Ramialison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg","family":"Heineke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hemal H.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia A.","family":"Rosenthal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena B.","family":"Furtado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3579-8625","authenticated-orcid":false,"given":"Mauro W.","family":"Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"5","key":"10.1016\/j.molmet.2018.11.002_bib1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s11897-016-0301-0","article-title":"Burden of heart failure in adults with congenital heart disease","volume":"13","author":"Alshawabkeh","year":"2016","journal-title":"Current Heart Failure Reports"},{"issue":"9","key":"10.1016\/j.molmet.2018.11.002_bib2","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1161\/CIRCULATIONAHA.113.008396","article-title":"Lifetime prevalence of congenital heart disease in the general population from 2000 to 2010","volume":"130","author":"Marelli","year":"2014","journal-title":"Circulation"},{"issue":"20","key":"10.1016\/j.molmet.2018.11.002_bib3","doi-asserted-by":"crossref","first-page":"e348","DOI":"10.1161\/CIR.0000000000000535","article-title":"Diagnosis and management of noncardiac complications in adults with congenital heart disease: a scientific statement from the American Heart Association","volume":"136","author":"Lui","year":"2017","journal-title":"Circulation"},{"issue":"8","key":"10.1016\/j.molmet.2018.11.002_bib4","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1001\/jama.2014.732","article-title":"Prevalence of childhood and adult obesity in the United States, 2011\u20132012","volume":"311","author":"Ogden","year":"2014","journal-title":"Journal of the American Medical Association"},{"issue":"4","key":"10.1016\/j.molmet.2018.11.002_bib5","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1161\/CIR.0000000000000366","article-title":"Executive summary: heart disease and stroke statistics--2016 update: a report from the American Heart Association","volume":"133","author":"Writing Group","year":"2016","journal-title":"Circulation"},{"issue":"7","key":"10.1016\/j.molmet.2018.11.002_bib6","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.cjca.2013.03.021","article-title":"Hypertension, obesity, and coronary artery disease in the survivors of congenital heart disease","volume":"29","author":"Roche","year":"2013","journal-title":"Canadian Journal of Cardiology"},{"issue":"8","key":"10.1016\/j.molmet.2018.11.002_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.cjca.2015.12.018","article-title":"Hospital readmission of patients with congenital heart disease in Canada","volume":"32","author":"Islam","year":"2016","journal-title":"Canadian Journal of Cardiology"},{"issue":"3","key":"10.1016\/j.molmet.2018.11.002_bib8","first-page":"238","article-title":"Functional characterization of a novel mutation in NKX2-5 associated with congenital heart disease and adult-onset cardiomyopathy","volume":"6","author":"Costa","year":"2013","journal-title":"Circulation: Cardiovascular Genetics"},{"issue":"6","key":"10.1016\/j.molmet.2018.11.002_bib9","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.88271","article-title":"Point mutations in murine Nkx2-5 phenocopy human congenital heart disease and induce pathogenic Wnt signaling","volume":"2","author":"Furtado","year":"2017","journal-title":"JCI Insight"},{"key":"10.1016\/j.molmet.2018.11.002_bib10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2342-10-1","article-title":"Design and validation of segment \u2013 freely available software for cardiovascular image analysis","volume":"10","author":"Heiberg","year":"2010","journal-title":"BMC Medical Imaging"},{"key":"10.1016\/j.molmet.2018.11.002_bib11","series-title":"Life in the cold","first-page":"431","article-title":"Mitochondria in the cold","author":"Gnaiger","year":"2000"},{"issue":"11","key":"10.1016\/j.molmet.2018.11.002_bib12","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1111\/febs.13733","article-title":"Oxidative phosphorylation and mitochondrial function differ between human prostate tissue and cultured cells","volume":"283","author":"Schopf","year":"2016","journal-title":"FEBS Journal"},{"key":"10.1016\/j.molmet.2018.11.002_bib13","doi-asserted-by":"crossref","first-page":"14.10.1","DOI":"10.1002\/cpbi.11","article-title":"Using MetaboAnalyst 3.0 for comprehensive metabolomics data analysis","volume":"55","author":"Xia","year":"2016","journal-title":"Current Protocols in Bioinformatics"},{"key":"10.1016\/j.molmet.2018.11.002_bib14","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1471-2105-10-11","article-title":"Filtering for increased power for microarray data analysis","volume":"10","author":"Hackstadt","year":"2009","journal-title":"BMC Bioinformatics"},{"issue":"13","key":"10.1016\/j.molmet.2018.11.002_bib15","doi-asserted-by":"crossref","first-page":"4281","DOI":"10.1021\/ac051632c","article-title":"Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics","volume":"78","author":"Dieterle","year":"2006","journal-title":"Analytical Chemistry"},{"issue":"7","key":"10.1016\/j.molmet.2018.11.002_bib16","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1172\/JCI62613","article-title":"Genetic variation in T-box binding element functionally affects SCN5A\/SCN10A enhancer","volume":"122","author":"van den Boogaard","year":"2012","journal-title":"Journal of Clinical Investigation"},{"issue":"5","key":"10.1016\/j.molmet.2018.11.002_bib17","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nbt.1630","article-title":"GREAT improves functional interpretation of cis-regulatory regions","volume":"28","author":"McLean","year":"2010","journal-title":"Nature Biotechnology"},{"issue":"1","key":"10.1016\/j.molmet.2018.11.002_bib18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet.journal"},{"issue":"1","key":"10.1016\/j.molmet.2018.11.002_bib19","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"issue":"2","key":"10.1016\/j.molmet.2018.11.002_bib20","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq \u2013 a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"issue":"2","key":"10.1016\/j.molmet.2018.11.002_bib21","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1186\/gb-2014-15-2-r29","article-title":"voom: precision weights unlock linear model analysis tools for RNA-seq read counts","volume":"15","author":"Law","year":"2014","journal-title":"Genome Biology"},{"issue":"7","key":"10.1016\/j.molmet.2018.11.002_bib22","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1002\/ejhf.304","article-title":"Heart failure with preserved ejection fraction: uncertainties and dilemmas","volume":"17","author":"Ferrari","year":"2015","journal-title":"European Journal of Heart Failure"},{"key":"10.1016\/j.molmet.2018.11.002_bib23","doi-asserted-by":"crossref","first-page":"21568","DOI":"10.1038\/srep21568","article-title":"Chronic consumption of a western diet induces robust glial activation in aging mice and in a mouse model of Alzheimer's disease","volume":"6","author":"Graham","year":"2016","journal-title":"Scientific Reports"},{"issue":"27","key":"10.1016\/j.molmet.2018.11.002_bib24","doi-asserted-by":"crossref","first-page":"24390","DOI":"10.1074\/jbc.M202490200","article-title":"The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism","volume":"277","author":"Dai","year":"2002","journal-title":"Journal of Biological Chemistry"},{"issue":"11","key":"10.1016\/j.molmet.2018.11.002_bib25","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/ncb2866","article-title":"Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure","volume":"15","author":"Dirkx","year":"2013","journal-title":"Nature Cell Biology"},{"key":"10.1016\/j.molmet.2018.11.002_bib26","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3389\/fphar.2015.00276","article-title":"The function of Rho-associated kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease","volume":"6","author":"Hartmann","year":"2015","journal-title":"Frontiers in Pharmacology"},{"issue":"8","key":"10.1016\/j.molmet.2018.11.002_bib27","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/nrm1983","article-title":"Regulation of cardiac hypertrophy by intracellular signalling pathways","volume":"7","author":"Heineke","year":"2006","journal-title":"Nature Reviews Molecular Cell Biology"},{"issue":"10","key":"10.1016\/j.molmet.2018.11.002_bib28","doi-asserted-by":"crossref","first-page":"3593","DOI":"10.1128\/MCB.23.10.3593-3606.2003","article-title":"Cardiac p300 is involved in myocyte growth with decompensated heart failure","volume":"23","author":"Yanazume","year":"2003","journal-title":"Molecular and Cellular Biology"},{"issue":"6","key":"10.1016\/j.molmet.2018.11.002_bib29","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1172\/JCI3949","article-title":"A\u00a0gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferator- activated receptor alpha- deficient mice","volume":"102","author":"Djouadi","year":"1998","journal-title":"Journal of Clinical Investigation"},{"issue":"15","key":"10.1016\/j.molmet.2018.11.002_bib30","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1161\/CIRCULATIONAHA.105.534594","article-title":"Decreased contractile and metabolic reserve in peroxisome proliferator-activated receptor-alpha-null hearts can be rescued by increasing glucose transport and utilization","volume":"112","author":"Luptak","year":"2005","journal-title":"Circulation"},{"issue":"1","key":"10.1016\/j.molmet.2018.11.002_bib31","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1152\/physrev.00015.2009","article-title":"Myocardial fatty acid metabolism in health and disease","volume":"90","author":"Lopaschuk","year":"2010","journal-title":"Physiological Reviews"},{"issue":"8","key":"10.1016\/j.molmet.2018.11.002_bib32","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1161\/CIRCULATIONAHA.115.017355","article-title":"The failing heart relies on ketone bodies as a fuel","volume":"133","author":"Aubert","year":"2016","journal-title":"Circulation"},{"issue":"Pt 1","key":"10.1016\/j.molmet.2018.11.002_bib33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1113\/jphysiol.2003.055095","article-title":"Energy metabolism in heart failure","volume":"555","author":"Ventura-Clapier","year":"2004","journal-title":"The Journal of Physiology"},{"issue":"6","key":"10.1016\/j.molmet.2018.11.002_bib34","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1161\/CIRCRESAHA.113.300376","article-title":"Cardiac metabolism in heart failure: implications beyond ATP production","volume":"113","author":"Doenst","year":"2013","journal-title":"Circulation Research"},{"issue":"5","key":"10.1016\/j.molmet.2018.11.002_bib35","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1161\/CIRCEP.115.002720","article-title":"A\u00a0mouse model of human congenital heart disease: progressive atrioventricular block induced by a heterozygous Nkx2-5 homeodomain missense mutation","volume":"8","author":"Chowdhury","year":"2015","journal-title":"Circulation Arrhythmia and Electrophysiology"},{"issue":"1","key":"10.1016\/j.molmet.2018.11.002_bib36","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/humu.9041","article-title":"Progressive AV-block and anomalous venous return among cardiac anomalies associated with two novel missense mutations in the CSX\/NKX2-5 gene","volume":"20","author":"Gutierrez-Roelens","year":"2002","journal-title":"Human Mutation"},{"issue":"8","key":"10.1016\/j.molmet.2018.11.002_bib37","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1172\/JCI19846","article-title":"Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system","volume":"113","author":"Jay","year":"2004","journal-title":"Journal of Clinical Investigation"},{"issue":"3","key":"10.1016\/j.molmet.2018.11.002_bib38","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0092-8674(04)00405-2","article-title":"Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block","volume":"117","author":"Pashmforoush","year":"2004","journal-title":"Cell"},{"issue":"4","key":"10.1016\/j.molmet.2018.11.002_bib39","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/cvr\/cvx017","article-title":"Metabolism in cardiomyopathy: every substrate matters","volume":"113","author":"Ritterhoff","year":"2017","journal-title":"Cardiovascular Research"},{"issue":"10","key":"10.1016\/j.molmet.2018.11.002_bib40","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1161\/RES.0000000000000097","article-title":"Assessing cardiac metabolism: a scientific statement from the American Heart Association","volume":"118","author":"Taegtmeyer","year":"2016","journal-title":"Circulation Research"},{"issue":"9","key":"10.1016\/j.molmet.2018.11.002_bib41","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"issue":"3","key":"10.1016\/j.molmet.2018.11.002_bib42","first-page":"297","article-title":"Metabolic origins of heart failure","volume":"2","author":"Wende","year":"2017","journal-title":"JACC: Basic to Translational Science"},{"issue":"3","key":"10.1016\/j.molmet.2018.11.002_bib43","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1172\/JCI24405","article-title":"Mitochondrial energy metabolism in heart failure: a question of balance","volume":"115","author":"Huss","year":"2005","journal-title":"Journal of Clinical Investigation"},{"issue":"4","key":"10.1016\/j.molmet.2018.11.002_bib44","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1159\/000369782","article-title":"Remodeling of glucose metabolism precedes pressure overload-induced left ventricular hypertrophy: review of a hypothesis","volume":"130","author":"Kundu","year":"2015","journal-title":"Cardiology"},{"issue":"1","key":"10.1016\/j.molmet.2018.11.002_bib45","doi-asserted-by":"crossref","first-page":"e1000582","DOI":"10.1371\/journal.pbio.1000582","article-title":"A\u00a0high-resolution anatomical atlas of the transcriptome in the mouse embryo","volume":"9","author":"Diez-Roux","year":"2011","journal-title":"PLoS Biology"},{"issue":"17","key":"10.1016\/j.molmet.2018.11.002_bib46","doi-asserted-by":"crossref","first-page":"8145","DOI":"10.1073\/pnas.90.17.8145","article-title":"Csx: a murine homeobox-containing gene specifically expressed in the developing heart","volume":"90","author":"Komuro","year":"1993","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"4","key":"10.1016\/j.molmet.2018.11.002_bib47","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1387\/ijdb.12141429","article-title":"Efficient Cre-mediated deletion in cardiac progenitor cells conferred by a 3'UTR-ires-Cre allele of the homeobox gene Nkx2-5","volume":"46","author":"Stanley","year":"2002","journal-title":"International Journal of Developmental Biology"},{"issue":"1","key":"10.1016\/j.molmet.2018.11.002_bib48","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1159\/000379749","article-title":"DuOx2 promoter regulation by hormones, transcriptional factors and the coactivator TAZ","volume":"4","author":"Cardoso-Weide","year":"2015","journal-title":"European Thyroid Journal"},{"issue":"4","key":"10.1016\/j.molmet.2018.11.002_bib49","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1210\/jc.2005-1350","article-title":"Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis","volume":"91","author":"Dentice","year":"2006","journal-title":"The Journal of Clinical Endocrinology and Metabolism"},{"issue":"6","key":"10.1016\/j.molmet.2018.11.002_bib50","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/art.40419","article-title":"Molecular basis for dysregulated activation of NKX2-5 in the vascular remodeling of systemic sclerosis","volume":"70","author":"Dritsoula","year":"2018","journal-title":"Arthritis & Rheumatology"},{"issue":"12","key":"10.1016\/j.molmet.2018.11.002_bib51","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.116.004440","article-title":"Nkx2-5 is expressed in atherosclerotic plaques and attenuates development of atherosclerosis in apolipoprotein E-deficient mice","volume":"5","author":"Du","year":"2016","journal-title":"Journal of the American Heart Association"},{"issue":"1","key":"10.1016\/j.molmet.2018.11.002_bib52","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCGENETICS.116.001564","article-title":"Effect of metformin on metabolites and relation with myocardial infarct size and left ventricular ejection fraction after myocardial infarction","volume":"10","author":"Eppinga","year":"2017","journal-title":"Circulation. Cardiovascular Genetics"},{"issue":"15","key":"10.1016\/j.molmet.2018.11.002_bib53","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1001\/jama.2014.3315","article-title":"Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial","volume":"311","author":"Lexis","year":"2014","journal-title":"Journal of the American Medical Association"},{"issue":"3","key":"10.1016\/j.molmet.2018.11.002_bib54","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nrendo.2013.256","article-title":"Metformin \u2013 mode of action and clinical implications for diabetes and cancer","volume":"10","author":"Pernicova","year":"2014","journal-title":"Nature Reviews Endocrinology"},{"key":"10.1016\/j.molmet.2018.11.002_bib55","doi-asserted-by":"crossref","first-page":"5813030","DOI":"10.1155\/2016\/5813030","article-title":"Metformin prevents fatty liver and improves balance of white\/brown adipose in an obesity mouse model by inducing FGF21","volume":"2016","author":"Kim","year":"2016","journal-title":"Mediators of Inflammation"},{"issue":"11","key":"10.1016\/j.molmet.2018.11.002_bib56","doi-asserted-by":"crossref","DOI":"10.3390\/ijms18112263","article-title":"Metformin potentiates the benefits of dietary restraint: a metabolomic study","volume":"18","author":"Riera-Borrull","year":"2017","journal-title":"International Journal of Molecular Sciences"},{"issue":"8","key":"10.1016\/j.molmet.2018.11.002_bib57","doi-asserted-by":"crossref","first-page":"E987","DOI":"10.1152\/ajpendo.00133.2013","article-title":"Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl\/6 mice","volume":"305","author":"Tajima","year":"2013","journal-title":"American Journal of Physiology. Endocrinology and Metabolism"},{"key":"10.1016\/j.molmet.2018.11.002_bib58","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1038\/ncomms3192","article-title":"Metformin improves healthspan and lifespan in mice","volume":"4","author":"Martin-Montalvo","year":"2013","journal-title":"Nature Communications"},{"issue":"9","key":"10.1016\/j.molmet.2018.11.002_bib59","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1007\/s00125-017-4349-5","article-title":"Metformin and ageing: improving ageing outcomes beyond glycaemic control","volume":"60","author":"Valencia","year":"2017","journal-title":"Diabetologia"},{"issue":"9","key":"10.1016\/j.molmet.2018.11.002_bib60","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1007\/s00125-017-4372-6","article-title":"Repurposing metformin for the prevention of cancer and cancer recurrence","volume":"60","author":"Heckman-Stoddard","year":"2017","journal-title":"Diabetologia"},{"issue":"9","key":"10.1016\/j.molmet.2018.11.002_bib61","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1007\/s00125-017-4337-9","article-title":"Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes","volume":"60","author":"Griffin","year":"2017","journal-title":"Diabetologia"},{"issue":"8","key":"10.1016\/j.molmet.2018.11.002_bib62","doi-asserted-by":"crossref","first-page":"e104888","DOI":"10.1371\/journal.pone.0104888","article-title":"Metformin protects cardiomyocyte from doxorubicin induced cytotoxicity through an AMP-activated protein kinase dependent signaling pathway: an in\u00a0vitro study","volume":"9","author":"Kobashigawa","year":"2014","journal-title":"PLoS One"},{"issue":"2","key":"10.1016\/j.molmet.2018.11.002_bib63","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.bbrc.2017.03.036","article-title":"Metformin improves cardiac function in mice with heart failure after myocardial infarction by regulating mitochondrial energy metabolism","volume":"486","author":"Sun","year":"2017","journal-title":"Biochemical and Biophysical Research Communications"},{"issue":"10","key":"10.1016\/j.molmet.2018.11.002_bib64","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/j.metabol.2016.06.012","article-title":"Metformin protects against infection-induced myocardial dysfunction","volume":"65","author":"Tzanavari","year":"2016","journal-title":"Metabolism"},{"issue":"2","key":"10.1016\/j.molmet.2018.11.002_bib65","doi-asserted-by":"crossref","DOI":"10.3390\/jpm8020014","article-title":"Genetic heterogeneity of SLC22 family of transporters in drug disposition","volume":"8","author":"Lozano","year":"2018","journal-title":"Journal of Personalized Medicine"},{"issue":"2","key":"10.1016\/j.molmet.2018.11.002_bib66","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1161\/CIRCULATIONAHA.115.019307","article-title":"Congenital heart defects in the United States: estimating the magnitude of the affected population in 2010","volume":"134","author":"Gilboa","year":"2016","journal-title":"Circulation"},{"issue":"2","key":"10.1016\/j.molmet.2018.11.002_bib67","doi-asserted-by":"crossref","first-page":"e001132","DOI":"10.1161\/JAHA.114.001132","article-title":"Metabolic syndrome in adults with congenital heart disease","volume":"5","author":"Deen","year":"2016","journal-title":"Journal of the American Heart Association"},{"issue":"5","key":"10.1016\/j.molmet.2018.11.002_bib68","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.cmet.2017.04.015","article-title":"Metabolic flexibility in health and disease","volume":"25","author":"Goodpaster","year":"2017","journal-title":"Cell Metabolism"},{"issue":"6","key":"10.1016\/j.molmet.2018.11.002_bib69","first-page":"H3270","article-title":"Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy","volume":"293","author":"Neglia","year":"2007","journal-title":"American Journal of Physiology: Heart and Circulatory Physiology"},{"issue":"4","key":"10.1016\/j.molmet.2018.11.002_bib70","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nrcardio.2016.203","article-title":"Expert consensus document: mitochondrial function as a therapeutic target in heart failure","volume":"14","author":"Brown","year":"2017","journal-title":"Nature Reviews Cardiology"}],"container-title":["Molecular Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877818308366?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877818308366?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T02:27:12Z","timestamp":1775269632000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2212877818308366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2]]},"references-count":70,"alternative-id":["S2212877818308366"],"URL":"https:\/\/doi.org\/10.1016\/j.molmet.2018.11.002","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/396416","asserted-by":"object"}]},"ISSN":["2212-8778"],"issn-type":[{"value":"2212-8778","type":"print"}],"subject":[],"published":{"date-parts":[[2019,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Metformin intervention prevents cardiac dysfunction in a murine model of adult congenital heart disease","name":"articletitle","label":"Article Title"},{"value":"Molecular Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molmet.2018.11.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 The Authors. Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}]}}