{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:25:09Z","timestamp":1792182309665,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T00:00:00Z","timestamp":1679097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL136601"],"award-info":[{"award-number":["R01HL136601"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL020948"],"award-info":[{"award-number":["HL020948"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["PRE835833"],"award-info":[{"award-number":["PRE835833"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Mounting evidence suggests that myocardial steatosis contributes to left ventricular diastolic dysfunction, but definitive evidence in humans is lacking due to confounding comorbidities. As such, we utilized a 48\u2010h food restriction model to acutely increase myocardial triglyceride (mTG) content \u2013 measured by <jats:sup>1<\/jats:sup>H magnetic resonance spectroscopy \u2013 in 27 young healthy volunteers (13\u00a0men\/14 women). Forty\u2010eight hours of fasting caused a more than 3\u2010fold increase in mTG content (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Diastolic function \u2013 defined as early diastolic circumferential strain rate (CSRd) \u2013 was unchanged following the 48\u2010h fasting intervention, but systolic circumferential strain rate was elevated (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), indicative of systolic\u2013diastolic uncoupling. Indeed, in a separate control experiment in 10 individuals, administration of low\u2010dose dobutamine (2\u00a0\u03bcg\/kg\/min) caused a similar change in systolic circumferential strain rate as was found during 48\u00a0h of food restriction, along with a proportionate increase in CSRd, such that the two metrics remained coupled. Taken together, these data indicate that myocardial steatosis contributes to diastolic dysfunction by impairing diastolic\u2013systolic coupling in healthy adults, and suggest that steatosis may contribute to the progression of heart disease.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15496-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Preclinical evidence strongly suggests that myocardial lipid accumulation (termed <jats:italic>steatosis<\/jats:italic>) is an important mechanism driving heart disease.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Definitive evidence in humans is limited due to the confounding influence of multiple underlying comorbidities.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using a 48\u2010h food restriction model to acutely increase myocardial triglyceride content in young healthy volunteers, we demonstrate an association between myocardial steatosis and left ventricular diastolic dysfunction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data advance the hypothesis that myocardial steatosis may contribute to diastolic dysfunction and suggest myocardial steatosis as a putative therapeutic target.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp284272","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T07:25:04Z","timestamp":1678346704000},"page":"1371-1382","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Myocardial steatosis impairs left ventricular diastolic\u2013systolic coupling in healthy humans"],"prefix":"10.1113","volume":"601","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8078-6810","authenticated-orcid":false,"given":"Andrew P.","family":"Oneglia","sequence":"first","affiliation":[{"name":"College of Nursing and Health Innovation, Department of Kinesiology University of Texas at Arlington  Arlington TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia S.","family":"Szczepaniak","sequence":"additional","affiliation":[{"name":"Biomedical Consulting in MRS  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manall F.","family":"Jaffery","sequence":"additional","affiliation":[{"name":"College of Nursing and Health Innovation, Department of Kinesiology University of Texas at Arlington  Arlington TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisha J.","family":"Cipher","sequence":"additional","affiliation":[{"name":"College of Nursing and Health Innovation, Department of Kinesiology University of Texas at Arlington  Arlington TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey G.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Center for Human Nutrition University of Texas Southwestern Medical Center  Dallas TX USA"},{"name":"Department of Molecular Genetics University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Haykowsky","sequence":"additional","affiliation":[{"name":"College of Health Sciences, Faculty of Nursing University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9298-047X","authenticated-orcid":false,"given":"Kerrie L.","family":"Moreau","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Clegg","sequence":"additional","affiliation":[{"name":"Texas Tech Health Sciences Center  El Paso TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlad","family":"Zaha","sequence":"additional","affiliation":[{"name":"Advanced Imaging Research Center University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3232-8639","authenticated-orcid":false,"given":"Michael D.","family":"Nelson","sequence":"additional","affiliation":[{"name":"College of Nursing and Health Innovation, Department of Kinesiology University of Texas at Arlington  Arlington TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,18]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.111.963751"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000154079.20681.B9"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10947"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0242"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi9924415"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.110.943522"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2009.04.022"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-018-0728-6"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0336724100"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214080"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.186809"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.160655"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.15.1868"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90413.2008"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2015"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10554-021-02483-x"},{"key":"e_1_2_5_18_1","volume-title":"Comparative Quantification of Health Risks: Global and Regional Burden of Disease Attributable to Selected Major Risk Factors","author":"James W.","year":"2003"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020245"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374578"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/echo.14975"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.645614"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-144-7-200604040-00011"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa245"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2014.04.024"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2013.05.036"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.036459"},{"key":"e_1_2_5_28_1","volume-title":"Obesity and overweight","author":"Organization W. H.","year":"2021"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00095.2005"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.07.062"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2021.10.017"},{"key":"e_1_2_5_32_1","first-page":"833","article-title":"Cardiac lipids by 1H MRS","author":"Szczepaniak L. S.","year":"2007","journal-title":"eMagRes"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0768"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00612.2015"},{"issue":"8","key":"e_1_2_5_35_1","first-page":"1315","article-title":"Immune correlates of diffuse myocardial fibrosis and diastolic dysfunction among aging women with human immunodeficiency virus","volume":"221","author":"Zanni M. V.","year":"2020","journal-title":"The Journal of Infectious Diseases"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.4.1784"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP284272","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP284272","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP284272","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T14:13:28Z","timestamp":1692627208000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP284272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,18]]},"references-count":35,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1113\/JP284272"],"URL":"https:\/\/doi.org\/10.1113\/jp284272","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,18]]},"assertion":[{"value":"2023-01-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}