Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis
Abstract Despite intensive research and constant medical progress, sepsis remains one of the most urgent unmet medical needs of today. Most studies have been focused on the inflammatory component of the disease; however, recent advances support the notion that sepsis is accompanied by extensive meta...
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| Format: | Article |
| Language: | English |
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Springer Nature
2020-01-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201911319 |
| _version_ | 1827015209702653952 |
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| author | Lise Van Wyngene Tineke Vanderhaeghen Steven Timmermans Jolien Vandewalle Kelly Van Looveren Jolien Souffriau Charlotte Wallaeys Melanie Eggermont Sam Ernst Evelien Van Hamme Amanda Gonçalves Guy Eelen Anneleen Remmerie Charlotte L Scott Caroline Rombouts Lynn Vanhaecke Liesbet De Bus Johan Decruyenaere Peter Carmeliet Claude Libert |
| author_facet | Lise Van Wyngene Tineke Vanderhaeghen Steven Timmermans Jolien Vandewalle Kelly Van Looveren Jolien Souffriau Charlotte Wallaeys Melanie Eggermont Sam Ernst Evelien Van Hamme Amanda Gonçalves Guy Eelen Anneleen Remmerie Charlotte L Scott Caroline Rombouts Lynn Vanhaecke Liesbet De Bus Johan Decruyenaere Peter Carmeliet Claude Libert |
| author_sort | Lise Van Wyngene |
| collection | DOAJ |
| description | Abstract Despite intensive research and constant medical progress, sepsis remains one of the most urgent unmet medical needs of today. 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 PPARα is crucial to coordinate the breakdown of fatty acids. The role of hepatic PPARα 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 PPARα levels, causing excess free fatty acids, leading to lipotoxicity, and glycerol. In addition, treatment of mice with the PPARα agonist pemafibrate protects against bacterial sepsis by improving hepatic PPARα 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. |
| first_indexed | 2024-03-07T17:01:57Z |
| format | Article |
| id | doaj.art-7138be713e384661805942f933a9d08d |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T14:18:52Z |
| publishDate | 2020-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-7138be713e384661805942f933a9d08d2024-10-28T08:55:39ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842020-01-0112212010.15252/emmm.201911319Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsisLise Van Wyngene0Tineke Vanderhaeghen1Steven Timmermans2Jolien Vandewalle3Kelly Van Looveren4Jolien Souffriau5Charlotte Wallaeys6Melanie Eggermont7Sam Ernst8Evelien Van Hamme9Amanda Gonçalves10Guy Eelen11Anneleen Remmerie12Charlotte L Scott13Caroline Rombouts14Lynn Vanhaecke15Liesbet De Bus16Johan Decruyenaere17Peter Carmeliet18Claude Libert19Center for Inflammation Research, VIBCenter for Inflammation Research, VIBCenter for Inflammation Research, VIBCenter for Inflammation Research, VIBCenter for Inflammation Research, VIBCenter for Inflammation Research, VIBCenter for Inflammation Research, VIBCenter for Inflammation Research, VIBCenter for Inflammation Research, VIBBio Imaging Core, VIB Center for Inflammation ResearchBio Imaging Core, VIB Center for Inflammation ResearchLaboratory of Angiogenesis and Vascular Biology, VIB Center for Cancer Biology, VIBCenter for Inflammation Research, VIBCenter for Inflammation Research, VIBFaculty of Veterinary Medicine, Department of Veterinary Public Health and Food Safety, Laboratory of Chemical Analysis, Ghent UniversityFaculty of Veterinary Medicine, Department of Veterinary Public Health and Food Safety, Laboratory of Chemical Analysis, Ghent UniversityDepartment of Critical Care Medicine, Ghent University HospitalDepartment of Critical Care Medicine, Ghent University HospitalLaboratory of Angiogenesis and Vascular Biology, VIB Center for Cancer Biology, VIBCenter for Inflammation Research, VIBAbstract Despite intensive research and constant medical progress, sepsis remains one of the most urgent unmet medical needs of today. 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 PPARα is crucial to coordinate the breakdown of fatty acids. The role of hepatic PPARα 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 PPARα levels, causing excess free fatty acids, leading to lipotoxicity, and glycerol. In addition, treatment of mice with the PPARα agonist pemafibrate protects against bacterial sepsis by improving hepatic PPARα 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.https://doi.org/10.15252/emmm.201911319fibrateslipid metabolismlipotoxicityliversepsis |
| spellingShingle | Lise Van Wyngene Tineke Vanderhaeghen Steven Timmermans Jolien Vandewalle Kelly Van Looveren Jolien Souffriau Charlotte Wallaeys Melanie Eggermont Sam Ernst Evelien Van Hamme Amanda Gonçalves Guy Eelen Anneleen Remmerie Charlotte L Scott Caroline Rombouts Lynn Vanhaecke Liesbet De Bus Johan Decruyenaere Peter Carmeliet Claude Libert Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis EMBO Molecular Medicine fibrates lipid metabolism lipotoxicity liver sepsis |
| title | Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis |
| title_full | Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis |
| title_fullStr | Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis |
| title_full_unstemmed | Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis |
| title_short | Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis |
| title_sort | hepatic pparα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis |
| topic | fibrates lipid metabolism lipotoxicity liver sepsis |
| url | https://doi.org/10.15252/emmm.201911319 |
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