{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:01:50Z","timestamp":1789506110532,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Special Research Fund of Ghent University (GOA and Methusalem Program)","award":["BOF.MET.2021.0001.0"],"award-info":[{"award-number":["BOF.MET.2021.0001.0"]}]},{"name":"the Special Research Fund of Ghent University (GOA and Methusalem Program)","award":["11Z2718N"],"award-info":[{"award-number":["11Z2718N"]}]},{"name":"the Special Research Fund of Ghent University (GOA and Methusalem Program)","award":["\/"],"award-info":[{"award-number":["\/"]}]},{"name":"FWO Vlaanderen","award":["BOF.MET.2021.0001.0"],"award-info":[{"award-number":["BOF.MET.2021.0001.0"]}]},{"name":"FWO Vlaanderen","award":["11Z2718N"],"award-info":[{"award-number":["11Z2718N"]}]},{"name":"FWO Vlaanderen","award":["\/"],"award-info":[{"award-number":["\/"]}]},{"name":"The Sigrid Jus\u00e9lius Foundation","award":["BOF.MET.2021.0001.0"],"award-info":[{"award-number":["BOF.MET.2021.0001.0"]}]},{"name":"The Sigrid Jus\u00e9lius Foundation","award":["11Z2718N"],"award-info":[{"award-number":["11Z2718N"]}]},{"name":"The Sigrid Jus\u00e9lius Foundation","award":["\/"],"award-info":[{"award-number":["\/"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Despite decades of research, sepsis remains one of the most urgent unmet medical needs. Mechanistic investigations into sepsis have mainly focused on targeting inflammatory pathways; however, recent data indicate that sepsis should also be seen as a metabolic disease. Targeting metabolic dysregulations that take place in sepsis might uncover novel therapeutic opportunities. The role of peroxisome proliferator-activated receptor alpha (PPAR\u0251) in liver dysfunction during sepsis has recently been described, and restoring PPAR\u0251 signaling has proven to be successful in mouse polymicrobial sepsis. To confirm that such therapy might be translated to septic patients, we analyzed metabolic perturbations in the liver of a porcine fecal peritonitis model. Resuscitation with fluids, vasopressor, antimicrobial therapy and abdominal lavage were applied to the pigs in order to mimic human clinical care. By using RNA-seq, we detected downregulated PPAR\u0251 signaling in the livers of septic pigs and that reduced PPAR\u0251 levels correlated well with disease severity. As PPAR\u0251 regulates the expression of many genes involved in fatty acid oxidation, the reduced expression of these target genes, concomitant with increased free fatty acids in plasma and ectopic lipid deposition in the liver, was observed. The results obtained with pigs are in agreement with earlier observations seen in mice and support the potential of targeting defective PPAR\u0251 signaling in clinical research.<\/jats:p>","DOI":"10.3390\/cells11244080","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T03:55:39Z","timestamp":1671162939000},"page":"4080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Hepatic Peroxisome Proliferator-Activated Receptor Alpha Dysfunction in Porcine Septic Shock"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1844-6476","authenticated-orcid":false,"given":"Jolien","family":"Vandewalle","sequence":"first","affiliation":[{"name":"VIB Center for Inflammation Research, VIB, 9052 Ghent, Belgium"},{"name":"Department for Biomedical Molecular Biology, Faculty of Sciences, Ghent University, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6650-1594","authenticated-orcid":false,"given":"Bruno","family":"Garcia","sequence":"additional","affiliation":[{"name":"Experimental Laboratory of Intensive Care, Universit\u00e9 Libre de Bruxelles, 1050 Brussels, Belgium"},{"name":"Department of Intensive Care, Centre Hospitalier Universitaire de Lille, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Timmermans","sequence":"additional","affiliation":[{"name":"VIB Center for Inflammation Research, VIB, 9052 Ghent, Belgium"},{"name":"Department for Biomedical Molecular Biology, Faculty of Sciences, Ghent University, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4227-2894","authenticated-orcid":false,"given":"Tineke","family":"Vanderhaeghen","sequence":"additional","affiliation":[{"name":"VIB Center for Inflammation Research, VIB, 9052 Ghent, Belgium"},{"name":"Department for Biomedical Molecular Biology, Faculty of Sciences, Ghent University, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise","family":"Van Wyngene","sequence":"additional","affiliation":[{"name":"VIB Center for Inflammation Research, VIB, 9052 Ghent, Belgium"},{"name":"Department for Biomedical Molecular Biology, Faculty of Sciences, Ghent University, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Eggermont","sequence":"additional","affiliation":[{"name":"VIB Center for Inflammation Research, VIB, 9052 Ghent, Belgium"},{"name":"Department for Biomedical Molecular Biology, Faculty of Sciences, Ghent University, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hester","family":"Dufoor","sequence":"additional","affiliation":[{"name":"VIB Center for Inflammation Research, VIB, 9052 Ghent, Belgium"},{"name":"Department for Biomedical Molecular Biology, Faculty of Sciences, Ghent University, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Van Dender","sequence":"additional","affiliation":[{"name":"VIB Center for Inflammation Research, VIB, 9052 Ghent, Belgium"},{"name":"Department for Biomedical Molecular Biology, Faculty of Sciences, Ghent University, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8702-6312","authenticated-orcid":false,"given":"F\u00ebllanza","family":"Halimi","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-3517","authenticated-orcid":false,"given":"Siska","family":"Croubels","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0981-0208","authenticated-orcid":false,"given":"Antoine","family":"Herpain","sequence":"additional","affiliation":[{"name":"Experimental Laboratory of Intensive Care, Universit\u00e9 Libre de Bruxelles, 1050 Brussels, Belgium"},{"name":"Department of Intensive Care, Erasme University Hospital\u2014HUB, Universit\u00e9 Libre de Bruxelles, 1050 Brussels, Belgium"},{"name":"Department of Intensive Care, St.-Pierre University Hospital, Universit\u00e9 Libre de Bruxelles, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6408-036X","authenticated-orcid":false,"given":"Claude","family":"Libert","sequence":"additional","affiliation":[{"name":"VIB Center for Inflammation Research, VIB, 9052 Ghent, Belgium"},{"name":"Department for Biomedical Molecular Biology, Faculty of Sciences, Ghent University, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, Regional, and National Sepsis Incidence and Mortality, 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