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Most studies have been focused on the inflammatory component of the disease; however, recent advances support the notion that sepsis is accompanied by extensive metabolic perturbations. During times of limited caloric intake and high energy needs, the liver acts as the central metabolic hub in which PPAR\u03b1 is crucial to coordinate the breakdown of fatty acids. The role of hepatic PPAR\u03b1 in liver dysfunction during sepsis has hardly been explored. We demonstrate that sepsis leads to a starvation response that is hindered by the rapid decline of hepatic PPAR\u03b1 levels, causing excess free fatty acids, leading to lipotoxicity, and glycerol. In addition, treatment of mice with the PPAR\u03b1 agonist pemafibrate protects against bacterial sepsis by improving hepatic PPAR\u03b1 function, reducing lipotoxicity and tissue damage. Since lipolysis is also increased in sepsis patients and pemafibrate protects after the onset of sepsis, these findings may point toward new therapeutic leads in sepsis.<\/jats:p>","DOI":"10.15252\/emmm.201911319","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T08:50:40Z","timestamp":1578559840000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Hepatic PPAR\u03b1 function and lipid metabolic pathways are dysregulated in polymicrobial sepsis"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9078-0113","authenticated-orcid":false,"given":"Lise","family":"Van Wyngene","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tineke","family":"Vanderhaeghen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Timmermans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1844-6476","authenticated-orcid":false,"given":"Jolien","family":"Vandewalle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Van Looveren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolien","family":"Souffriau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Wallaeys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Eggermont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Ernst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien","family":"Van Hamme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3354-5819","authenticated-orcid":false,"given":"Guy","family":"Eelen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneleen","family":"Remmerie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte L","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Rombouts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Vanhaecke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbet","family":"De Bus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3655-4318","authenticated-orcid":false,"given":"Johan","family":"Decruyenaere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7961-1821","authenticated-orcid":false,"given":"Peter","family":"Carmeliet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6408-036X","authenticated-orcid":false,"given":"Claude","family":"Libert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,9]]},"reference":[{"key":"BFEMMM201911319_CR1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/00000658-198001000-00008","volume":"191","author":"J Askanazi","year":"1980","unstructured":"Askanazi J, Carpentier YA, Elwyn DH, Nordenstrom J, Jeevanandam M, Rosenbaum SH, Gump FE, Kinney JM (1980) Influence of total parenteral nutrition on fuel utilization in injury and sepsis. 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