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Donor shortages necessitate the use of higher risk donor livers, including fatty livers, which are more susceptible to ischemia\u2010reperfusion injury. Machine perfusion has improved graft utilization and is typically performed at hypothermic (8\u201312\u00b0C) or normothermic (35\u201337\u00b0C) temperatures. Here we studied the impact of mild hyperthermia (40\u00b0C) as a therapeutic intervention for fatty livers using in\u2010depth proteomic and lipoprotein profiling of whole organ perfusion and precision\u2010cut liver slices. We observed proteomic changes with metabolic alterations over time, evidenced by a significant increase in lipid export in whole organ perfusions. Furthermore, PCLS showed significant upregulation of metabolic processes and heat shock protein response after 24\u2009h of hyperthermia. Machine perfusion under hyperthermic conditions may be a potential strategy to improve the utilization of fatty liver grafts, ultimately expanding the donor pool and improving transplant outcomes.<\/jats:p>","DOI":"10.14814\/phy2.70348","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T01:37:43Z","timestamp":1747273063000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Therapeutic hyperthermia promotes lipid export and\n                    <scp>HSP70<\/scp>\n                    \/90 during machine perfusion of human livers"],"prefix":"10.14814","volume":"13","author":[{"given":"Adam M.","family":"Thorne","sequence":"first","affiliation":[{"name":"Department of Liver Transplantation and HPB Surgery University of Groningen and University Medical Center Groningen  Groningen The 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University of Groningen University of Groningen and University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Porte","sequence":"additional","affiliation":[{"name":"Department of Liver Transplantation and HPB Surgery University of Groningen and University Medical Center Groningen  Groningen The Netherlands"},{"name":"Erasmus MC Transplant Institute, Department of Surgery, Division of HPB and Transplant Surgery University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folkert","family":"Kuipers","sequence":"additional","affiliation":[{"name":"European Research Institute for the Biology of Ageing (ERIBA) University of Groningen and University Medical Center Groningen  Groningen The 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