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Urolithin A (UA; 3,8\u2010dihydroxy\u20106H\u2010dibenzopyran\u20106\u2010one), a natural polyphenolic compound, has been extensively studied and shown to possess significant anti\u2010inflammatory effects. Nevertheless, the specific effects of UA in SAP\u2010associated acute cardiac injury (SACI) have not been definitively elucidated. Here, we investigated the therapeutic role and mechanisms of UA in SACI using transcriptomics and untargeted metabolomics analyses in a mouse model of SACI and in vitro studies. SACI resulted in severely damaged pancreatic and cardiac tissues with myocardial mitochondrial dysfunction and mitochondrial metabolism disorders. UA significantly reduced the levels of lipase, amylase and inflammatory factors, attenuated pathological damage to pancreatic and cardiac tissues, and reduced myocardial cell apoptosis and oxidative stress in SACI. Moreover, UA increased mitochondrial membrane potential and adenosine triphosphate production and restored mitochondrial metabolism, but the efficacy of UA was weakened by the inhibition of CPT1. Therefore, UA can attenuate cardiac mitochondrial dysfunction and reduce myocardial apoptosis by restoring the balance of mitochondrial fatty acid oxidation metabolism. CPT1 may be a potential target. This study has substantial implications for advancing our understanding of the pathogenesis and drug development of SACI.<\/jats:p>","DOI":"10.1002\/mco2.459","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T11:05:37Z","timestamp":1702983937000},"source":"Crossref","is-referenced-by-count":21,"title":["Urolithin A protects severe acute pancreatitis\u2010associated acute cardiac injury by regulating mitochondrial fatty acid oxidative metabolism in cardiomyocytes"],"prefix":"10.1002","volume":"4","author":[{"given":"Yue","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine West China Hospital of Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine West China Hospital of Sichuan University  Chengdu 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