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However, whether an increased ketone body supply in hypoxic cardiomyocytes and ischemic hearts is protective or not remains elusive. The goal of this study is to determine the effect of \u03b2-hydroxybutyrate (\u03b2-OHB), the main constituent of ketone bodies, on cardiomyocytes under hypoxic conditions and the effects of ketogenic diet (KD) on cardiac function in a myocardial infarction (MI) mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human peripheral blood collected from patients with acute myocardial infarction and healthy volunteers was used to detect the level of \u03b2-OHB. N-terminal proB-type natriuretic peptide (NT-proBNP) levels and left ventricular ejection fractions (LVEFs) were measured to study the relationship between plasma \u03b2-OHB and cardiac function. Adult mouse cardiomyocytes and MI mouse models fed a KD were used to research the effect of \u03b2-OHB on cardiac damage. qPCR, western blot analysis, and immunofluorescence were used to detect the interaction between \u03b2-OHB and glycolysis. Live\/dead cell staining and imaging, lactate dehydrogenase, Cell Counting Kit-8 assays, echocardiography, and 2,3,5-triphenyltetrazolium chloride staining were performed to evaluate the cardiomyocyte death, cardiac function, and infarct sizes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>\u03b2-OHB level was significantly higher in acute MI patients and MI mice. Treatment with \u03b2-OHB exacerbated cardiomyocyte death and decreased glucose absorption and glycolysis under hypoxic conditions. These effects were partially ameliorated by inhibiting hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) degradation via roxadustat administration in hypoxia-stimulated cardiomyocytes. Furthermore, \u03b2-OHB metabolisms were obscured in cardiomyocytes under hypoxic conditions. Additionally, MI mice fed a KD exhibited exacerbated cardiac dysfunction compared with control chow diet (CD)-fed MI mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Elevated \u03b2-OHB levels may be maladaptive to the heart under hypoxic\/ischemic conditions. Administration of roxadustat can partially reverse these harmful effects by stabilizing HIF-1\u03b1 and inducing a metabolic shift toward glycolysis for energy production.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10557-021-07267-y","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T14:28:36Z","timestamp":1634308116000},"page":"383-397","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["\u03b2-Hydroxybutyrate Exacerbates Hypoxic Injury by Inhibiting HIF-1\u03b1-Dependent Glycolysis in Cardiomyocytes\u2014Adding Fuel to the Fire?"],"prefix":"10.1007","volume":"36","author":[{"given":"Xiurui","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rifeng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilan","family":"A","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"issue":"2","key":"7267_CR1","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.cmet.2016.11.005","volume":"25","author":"T Li","year":"2017","unstructured":"Li T, Zhang Z, Kolwicz SC, et al. 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Cell Metab. 2015;21(1):65\u201380.","journal-title":"Cell Metab"}],"container-title":["Cardiovascular Drugs and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10557-021-07267-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10557-021-07267-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10557-021-07267-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T06:21:20Z","timestamp":1699683680000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10557-021-07267-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,15]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["7267"],"URL":"https:\/\/doi.org\/10.1007\/s10557-021-07267-y","relation":{},"ISSN":["0920-3206","1573-7241"],"issn-type":[{"value":"0920-3206","type":"print"},{"value":"1573-7241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,15]]},"assertion":[{"value":"16 September 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal protocols performed in this study were approved by and complied with the guides of the Animal Care and Use Committee of the Zhongshan Hospital, Fudan University.All patients\u2019 information was obtained from hospital medical records, test databases, or direct interviews with patients. The study protocol was approved by the Ethics Committee of Shanxi Cardiovascular Hospital (clinical registry number: 2019007).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Informed consent was obtained from all individual participants included in the study, and the written informed consent was provided by each patient at the time of registration.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}