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Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis

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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 PPAR alpha is crucial to coordinate the breakdown of fatty acids. The role of hepatic PPAR alpha 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 alpha levels, causing excess free fatty acids, leading to lipotoxicity, and glycerol. In addition, treatment of mice with the PPAR alpha agonist pemafibrate protects against bacterial sepsis by improving hepatic PPAR alpha 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.
Keywords
fibrates, lipid metabolism, lipotoxicity, liver, sepsis, FATTY-ACID OXIDATION, INFLAMMATORY RESPONSE, CECAL LIGATION, EXPRESSION, LIVER, RECEPTORS, TISSUE, PHASE, FENOFIBRATE, DYSFUNCTION

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MLA
Van Wyngene, Lise, et al. “Hepatic PPARα Function and Lipid Metabolic Pathways Are Dysregulated in Polymicrobial Sepsis.” EMBO MOLECULAR MEDICINE, vol. 12, no. 2, 2020, doi:10.15252/emmm.201911319.
APA
Van Wyngene, L., Vanderhaeghen, T., Timmermans, S., Vandewalle, J., Van Looveren, K., Souffriau, J., … Libert, C. (2020). Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis. EMBO MOLECULAR MEDICINE, 12(2). https://doi.org/10.15252/emmm.201911319
Chicago author-date
Van Wyngene, Lise, Tineke Vanderhaeghen, Steven Timmermans, Jolien Vandewalle, Kelly Van Looveren, Jolien Souffriau, Charlotte Wallaeys, et al. 2020. “Hepatic PPARα Function and Lipid Metabolic Pathways Are Dysregulated in Polymicrobial Sepsis.” EMBO MOLECULAR MEDICINE 12 (2). https://doi.org/10.15252/emmm.201911319.
Chicago author-date (all authors)
Van Wyngene, Lise, 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 Scott, Caroline Rombouts, Lynn Vanhaecke, Liesbet De Bus, Johan Decruyenaere, Peter Carmeliet, and Claude Libert. 2020. “Hepatic PPARα Function and Lipid Metabolic Pathways Are Dysregulated in Polymicrobial Sepsis.” EMBO MOLECULAR MEDICINE 12 (2). doi:10.15252/emmm.201911319.
Vancouver
1.
Van Wyngene L, Vanderhaeghen T, Timmermans S, Vandewalle J, Van Looveren K, Souffriau J, et al. Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis. EMBO MOLECULAR MEDICINE. 2020;12(2).
IEEE
[1]
L. Van Wyngene et al., “Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis,” EMBO MOLECULAR MEDICINE, vol. 12, no. 2, 2020.
@article{8642440,
  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 PPAR alpha is crucial to coordinate the breakdown of fatty acids. The role of hepatic PPAR alpha 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 alpha levels, causing excess free fatty acids, leading to lipotoxicity, and glycerol. In addition, treatment of mice with the PPAR alpha agonist pemafibrate protects against bacterial sepsis by improving hepatic PPAR alpha 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.}},
  articleno    = {{e11319}},
  author       = {{Van Wyngene, Lise and Vanderhaeghen, Tineke and Timmermans, Steven and Vandewalle, Jolien and Van Looveren, Kelly and Souffriau, Jolien and Wallaeys, Charlotte and Eggermont, Melanie and Ernst, Sam and Van Hamme, Evelien and Gonçalves, Amanda and Eelen, Guy and Remmerie, Anneleen and Scott, Charlotte and Rombouts, Caroline and Vanhaecke, Lynn and De Bus, Liesbet and Decruyenaere, Johan and Carmeliet, Peter and Libert, Claude}},
  issn         = {{1757-4676}},
  journal      = {{EMBO MOLECULAR MEDICINE}},
  keywords     = {{fibrates,lipid metabolism,lipotoxicity,liver,sepsis,FATTY-ACID OXIDATION,INFLAMMATORY RESPONSE,CECAL LIGATION,EXPRESSION,LIVER,RECEPTORS,TISSUE,PHASE,FENOFIBRATE,DYSFUNCTION}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{20}},
  title        = {{Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis}},
  url          = {{http://dx.doi.org/10.15252/emmm.201911319}},
  volume       = {{12}},
  year         = {{2020}},
}

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