{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:13:31Z","timestamp":1792271611664,"version":"4.4.0"},"reference-count":109,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01HL52251"],"award-info":[{"award-number":["R01HL52251"]}]},{"name":"National Institute of Health","award":["R01HL151239"],"award-info":[{"award-number":["R01HL151239"]}]},{"DOI":"10.13039\/100005188","name":"TRDRP","doi-asserted-by":"publisher","award":["T31IP1606"],"award-info":[{"award-number":["T31IP1606"]}],"id":[{"id":"10.13039\/100005188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R396-2022-189"],"award-info":[{"award-number":["R396-2022-189"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF22OC0079368"],"award-info":[{"award-number":["NNF22OC0079368"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004836","name":"Danmarks Frie Forskningsfond","doi-asserted-by":"publisher","award":["DFF 3165-00028A"],"award-info":[{"award-number":["DFF 3165-00028A"]}],"id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007605","name":"Aarhus University","doi-asserted-by":"publisher","award":["AUFF-E-2022-7-9"],"award-info":[{"award-number":["AUFF-E-2022-7-9"]}],"id":[{"id":"10.13039\/100007605","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This comprehensive review explores the critical role of fatty acid (FA) metabolism in cardiac diseases, particularly heart failure (HF), and the implications for therapeutic strategies. The heart\u2019s reliance on ATP, primarily sourced from mitochondrial oxidative metabolism, underscores the significance of metabolic flexibility, with fatty acid oxidation (FAO) being a dominant source. In HF, metabolic shifts occur with an altered FA uptake and FAO, impacting mitochondrial function and contributing to disease progression. Conditions like obesity and diabetes also lead to metabolic disturbances, resulting in cardiomyopathy marked by an over-reliance on FAO, mitochondrial dysfunction, and lipotoxicity. Therapeutic approaches targeting FA metabolism in cardiac diseases have evolved, focusing on inhibiting or stimulating FAO to optimize cardiac energetics. Strategies include using CPT1A inhibitors, using PPAR\u03b1 agonists, and enhancing mitochondrial biogenesis and function. However, the effectiveness varies, reflecting the complexity of metabolic remodeling in HF. Hence, treatment strategies should be individualized, considering that cardiac energy metabolism is intricate and tightly regulated. The therapeutic aim is to optimize overall metabolic function, recognizing the pivotal role of FAs and the need for further research to develop effective therapies, with promising new approaches targeting mitochondrial oxidative metabolism and FAO that improve cardiac function.<\/jats:p>","DOI":"10.3390\/ijms25021211","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T03:33:41Z","timestamp":1705635221000},"page":"1211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Metabolic Flexibility of the Heart: The Role of Fatty Acid Metabolism in Health, Heart Failure, and Cardiometabolic Diseases"],"prefix":"10.3390","volume":"25","author":[{"given":"Virginia","family":"Actis Dato","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9361-6602","authenticated-orcid":false,"given":"Stephan","family":"Lange","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"Department of Biomedicine, Aarhus University, DK 8000 Aarhus, Denmark"},{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, DK 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7161-3248","authenticated-orcid":false,"given":"Yoshitake","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fcvm.2018.00068","article-title":"Loss of Metabolic Flexibility in the Failing Heart","volume":"5","author":"Karwi","year":"2018","journal-title":"Front. 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