{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:38:13Z","timestamp":1785181093268,"version":"3.55.0"},"reference-count":102,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:p>Diabetic cardiomyopathy was first defined over four decades ago. It was observed in small post-mortem studies of diabetic patients who suffered from concomitant heart failure despite the absence of hypertension, coronary disease or other likely causal factors, as well as in large population studies such as the Framingham Heart Study. Subsequent studies continue to demonstrate an increased incidence of heart failure in the setting of diabetes independent of established risk factors, suggesting direct effects of diabetes on the myocardium. Impairments in glucose metabolism and handling receive the majority of the blame. The role of concomitant impairments in lipid handling, particularly at the level of the myocardium, has however received much less attention. Cardiac lipid accumulation commonly occurs in the setting of type 2 diabetes and has been suggested to play a direct causal role in the development of cardiomyopathy and heart failure in a process termed as cardiac lipotoxicity. Excess lipids promote numerous pathological processes linked to the development of cardiomyopathy, including mitochondrial dysfunction and inflammation. Although somewhat underappreciated, cardiac lipotoxicity also occurs in the setting of type 1 diabetes. This phenomenon is, however, largely understudied in comparison to hyperglycaemia, which has been widely studied in this context. The current review addresses the changes in lipid metabolism occurring in the type 1 diabetic heart and how they are implicated in disease progression. Furthermore, the pathological pathways linked to cardiac lipotoxicity are discussed. Finally, we consider novel approaches for modulating lipid metabolism as a cardioprotective mechanism against cardiomyopathy and heart failure.<\/jats:p>","DOI":"10.1530\/jme-16-0249","type":"journal-article","created":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T20:37:20Z","timestamp":1491251840000},"page":"R225-R240","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":66,"title":["Lipid metabolism and its implications for type 1 diabetes-associated cardiomyopathy"],"prefix":"10.1530","volume":"58","author":[{"given":"Rebecca H","family":"Ritchie","sequence":"first","affiliation":[{"name":"1Heart Failure PharmacologyBaker Heart & Diabetes Institute, Melbourne, Victoria, Australia"},{"name":"2Central Clinical SchoolMonash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eser J","family":"Zerenturk","sequence":"additional","affiliation":[{"name":"3Lipid Metabolism & Cardiometabolic Disease LaboratoryBaker Heart & Diabetes Institute, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darnel","family":"Prakoso","sequence":"additional","affiliation":[{"name":"1Heart Failure PharmacologyBaker Heart & Diabetes Institute, Melbourne, Victoria, Australia"},{"name":"4School of BiosciencesThe University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna C","family":"Calkin","sequence":"additional","affiliation":[{"name":"2Central Clinical SchoolMonash University, Melbourne, Victoria, Australia"},{"name":"3Lipid Metabolism & Cardiometabolic Disease LaboratoryBaker Heart & Diabetes Institute, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2017050417102396000_58.4.R225.1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-S062"},{"key":"2017050417102396000_58.4.R225.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.07.031"},{"key":"2017050417102396000_58.4.R225.3","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-126-4-199702150-00006"},{"key":"2017050417102396000_58.4.R225.4","first-page":"18","article-title":"Myocardial metabolism in insulin-deficient diabetic humans without coronary artery disease","volume":"258","author":"Avogaro","year":"1990","journal-title":"American Journal of Physiology"},{"key":"2017050417102396000_58.4.R225.5","first-page":"65","article-title":"Reversal of mitochondrial proteomic loss in Type 1 diabetic heart with overexpression of phospholipid hydroperoxide glutathione peroxidase","volume":"304","author":"Baseler","year":"2013","journal-title":"American Journal of Physiology: Regulatory, Integrative and Comparative Physiology"},{"key":"2017050417102396000_58.4.R225.6","first-page":"108","article-title":"Type 1 diabetic cardiomyopathy in the Akita (Ins2WT\/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function","volume":"297","author":"Basu","year":"2009","journal-title":"American Journal of Physiology: Heart and Circulatory Physiology"},{"key":"2017050417102396000_58.4.R225.7","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000433"},{"key":"2017050417102396000_58.4.R225.8","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(54)90365-4"},{"key":"2017050417102396000_58.4.R225.9","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.679597"},{"key":"2017050417102396000_58.4.R225.10","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3171-6"},{"key":"2017050417102396000_58.4.R225.11","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0079"},{"key":"2017050417102396000_58.4.R225.12","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0259"},{"key":"2017050417102396000_58.4.R225.13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32578"},{"key":"2017050417102396000_58.4.R225.14","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-013-9679-4"},{"key":"2017050417102396000_58.4.R225.15","first-page":"42","article-title":"TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes","volume":"303","author":"Dong","year":"2012","journal-title":"American Journal of Physiology: Heart and Circulatory Physiology"},{"key":"2017050417102396000_58.4.R225.16","doi-asserted-by":"publisher","unstructured":"Doria A Nosadini R Avogaro A Fioretto P Crepaldi G 1991 Myocardial metabolism in type 1 diabetic patients without coronary artery disease. Diabetic Medicine 8 Spec No 7.","DOI":"10.1111\/j.1464-5491.1991.tb02168.x"},{"key":"2017050417102396000_58.4.R225.17","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90505-9"},{"key":"2017050417102396000_58.4.R225.18","doi-asserted-by":"publisher","DOI":"10.1210\/en.130.3.1387"},{"key":"2017050417102396000_58.4.R225.19","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0012"},{"key":"2017050417102396000_58.4.R225.20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200214080"},{"key":"2017050417102396000_58.4.R225.21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0336724100"},{"key":"2017050417102396000_58.4.R225.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2004.07.008"},{"key":"2017050417102396000_58.4.R225.23","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00238-0"},{"key":"2017050417102396000_58.4.R225.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2012.04.009"},{"key":"2017050417102396000_58.4.R225.25","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1817"},{"key":"2017050417102396000_58.4.R225.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.04.006"},{"key":"2017050417102396000_58.4.R225.27","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199609)13:9<834::AID-DIA225>3.0.CO;2-M"},{"key":"2017050417102396000_58.4.R225.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.01.141"},{"key":"2017050417102396000_58.4.R225.29","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-0513"},{"key":"2017050417102396000_58.4.R225.30","doi-asserted-by":"publisher","DOI":"10.1021\/bi7004015"},{"key":"2017050417102396000_58.4.R225.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.09.030"},{"key":"2017050417102396000_58.4.R225.32","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1456"},{"key":"2017050417102396000_58.4.R225.33","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.pharmthera.2014.01.003","article-title":"Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways","volume":"142","author":"Huynh","year":"2014","journal-title":"Pharmacology and Therapeutics"},{"key":"2017050417102396000_58.4.R225.34","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.22.2668"},{"key":"2017050417102396000_58.4.R225.35","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3230"},{"key":"2017050417102396000_58.4.R225.36","doi-asserted-by":"publisher","DOI":"10.1021\/bi00037a034"},{"key":"2017050417102396000_58.4.R225.37","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1979.03290450033020"},{"key":"2017050417102396000_58.4.R225.38","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(74)90089-7"},{"key":"2017050417102396000_58.4.R225.39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.6.2211"},{"key":"2017050417102396000_58.4.R225.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.10.013"},{"key":"2017050417102396000_58.4.R225.41","doi-asserted-by":"publisher","DOI":"10.1385\/CT:5:3:285"},{"key":"2017050417102396000_58.4.R225.42","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00133-14"},{"key":"2017050417102396000_58.4.R225.43","first-page":"973","article-title":"Three cases of acute pulmonary thromboembolism diagnosed by transesophageal echocardiography","volume":"57","author":"Kusaka","year":"2008","journal-title":"Masui"},{"key":"2017050417102396000_58.4.R225.44","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01198.2011"},{"key":"2017050417102396000_58.4.R225.45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1994.tb00799.x"},{"key":"2017050417102396000_58.4.R225.46","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1333"},{"key":"2017050417102396000_58.4.R225.47","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.1.174"},{"key":"2017050417102396000_58.4.R225.48","first-page":"1035","article-title":"Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy","volume":"17","author":"Ligeti","year":"2006","journal-title":"International Journal of Molecular Medicine"},{"key":"2017050417102396000_58.4.R225.49","doi-asserted-by":"publisher","DOI":"10.1161\/hh0901.089881"},{"key":"2017050417102396000_58.4.R225.50","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1629"},{"key":"2017050417102396000_58.4.R225.51","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.92.11.3240"},{"key":"2017050417102396000_58.4.R225.52","first-page":"1","article-title":"Breeding of a non-obese, diabetic strain of mice","volume":"29","author":"Makino","year":"1980","journal-title":"Jikken Dobutsu"},{"key":"2017050417102396000_58.4.R225.53","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.645614"},{"key":"2017050417102396000_58.4.R225.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.09.006"},{"key":"2017050417102396000_58.4.R225.55","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203458200"},{"key":"2017050417102396000_58.4.R225.56","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M060061"},{"key":"2017050417102396000_58.4.R225.57","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.193995"},{"key":"2017050417102396000_58.4.R225.58","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1199"},{"key":"2017050417102396000_58.4.R225.59","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000207406.94146.c2"},{"key":"2017050417102396000_58.4.R225.60","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3389\/fphys.2016.00093","article-title":"Ablation of matrix metalloproteinase-9 prevents cardiomyocytes contractile dysfunction in diabetics","volume":"7","author":"Prathipati","year":"2016","journal-title":"Frontiers in Physiology"},{"key":"2017050417102396000_58.4.R225.61","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0927"},{"key":"2017050417102396000_58.4.R225.62","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(63)91500-9"},{"key":"2017050417102396000_58.4.R225.63","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108843"},{"key":"2017050417102396000_58.4.R225.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.07.062"},{"key":"2017050417102396000_58.4.R225.65","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.6.2485"},{"key":"2017050417102396000_58.4.R225.66","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(72)90595-4"},{"key":"2017050417102396000_58.4.R225.67","doi-asserted-by":"publisher","DOI":"10.2337\/db15-0238"},{"key":"2017050417102396000_58.4.R225.68","doi-asserted-by":"crossref","first-page":"3941","DOI":"10.1002\/j.1460-2075.1991.tb04964.x","article-title":"Targeted integration of adeno-associated virus (AAV) into human chromosome 19","volume":"10","author":"Samulski","year":"1991","journal-title":"EMBO Journal"},{"key":"2017050417102396000_58.4.R225.69","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.306842"},{"key":"2017050417102396000_58.4.R225.70","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2263com"},{"key":"2017050417102396000_58.4.R225.71","first-page":"905","article-title":"Cardiac mitochondrial damage and biogenesis in a chronic model of type 1 diabetes","volume":"287","author":"Shen","year":"2004","journal-title":"American Journal of Physiology: Endocrinology and Metabolism"},{"key":"2017050417102396000_58.4.R225.72","first-page":"379","article-title":"Cardiomyocyte defects in diabetic models and protection with cardiac-targeted transgenes","volume":"112","author":"Shen","year":"2005","journal-title":"Methods in Molecular Medicine"},{"key":"2017050417102396000_58.4.R225.73","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.03.06.db05-1039"},{"key":"2017050417102396000_58.4.R225.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2004.10.018"},{"key":"2017050417102396000_58.4.R225.75","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1900\/RDS.2007.4.159","article-title":"Diabetic cardiomyopathy in OVE26 mice shows mitochondrial ROS production and divergence between in vivo and in vitro contractility","volume":"4","author":"Song","year":"2007","journal-title":"Review of Diabetic Studies"},{"key":"2017050417102396000_58.4.R225.76","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207217200"},{"key":"2017050417102396000_58.4.R225.77","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.213199"},{"key":"2017050417102396000_58.4.R225.78","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10372"},{"key":"2017050417102396000_58.4.R225.79","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.160457"},{"key":"2017050417102396000_58.4.R225.80","doi-asserted-by":"publisher","DOI":"10.1042\/CS20120448"},{"key":"2017050417102396000_58.4.R225.81","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.316.7134.823"},{"key":"2017050417102396000_58.4.R225.82","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00016.2008"},{"key":"2017050417102396000_58.4.R225.83","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)07019-6"},{"key":"2017050417102396000_58.4.R225.84","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121038"},{"key":"2017050417102396000_58.4.R225.85","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4431"},{"key":"2017050417102396000_58.4.R225.86","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00650.2012"},{"key":"2017050417102396000_58.4.R225.87","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0329"},{"key":"2017050417102396000_58.4.R225.88","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114616"},{"key":"2017050417102396000_58.4.R225.89","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2005.12.009"},{"key":"2017050417102396000_58.4.R225.90","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0351"},{"key":"2017050417102396000_58.4.R225.91","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.474650"},{"key":"2017050417102396000_58.4.R225.92","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200316751"},{"key":"2017050417102396000_58.4.R225.93","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12530"},{"key":"2017050417102396000_58.4.R225.94","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000264104.25265.b6"},{"key":"2017050417102396000_58.4.R225.95","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0801"},{"key":"2017050417102396000_58.4.R225.96","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.3.777"},{"key":"2017050417102396000_58.4.R225.97","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.5.1336"},{"key":"2017050417102396000_58.4.R225.98","doi-asserted-by":"publisher","DOI":"10.2337\/diab.46.5.887"},{"key":"2017050417102396000_58.4.R225.99","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1097\/01.LAB.0000027921.01548.C5","article-title":"Calmodulin overexpression causes Ca(2+)-dependent apoptosis of pancreatic beta cells, which can be prevented by inhibition of nitric oxide synthase","volume":"82","author":"Yu","year":"2002","journal-title":"Laboratory Investigation"},{"key":"2017050417102396000_58.4.R225.100","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302331"},{"key":"2017050417102396000_58.4.R225.101","doi-asserted-by":"publisher","DOI":"10.1081\/ERC-120022318"},{"key":"2017050417102396000_58.4.R225.102","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2009.09.014"}],"container-title":["Journal of Molecular Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/jme.bioscientifica.com\/view\/journals\/jme\/58\/4\/R225.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1530\/JME-16-0249","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:53:07Z","timestamp":1784555587000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/jme\/article\/58\/4\/R225-R240\/11607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5]]},"references-count":102,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1530\/jme-16-0249","relation":{},"ISSN":["0952-5041","1479-6813"],"issn-type":[{"value":"0952-5041","type":"print"},{"value":"1479-6813","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5]]}}}