title: Short-term high fat feeding increases organ injury and mortality after polymicrobial sepsis.
abstract: The purpose of this study was to examine the effect of short-term high fat feeding on the inflammatory response in polymicrobial sepsis. Male C57BL/6 mice at 6 weeks of age were randomized to a high-fat diet (HFD) (60% kcal fat) or control diet (CD) (16% kcal fat) for 3 weeks. After 3 weeks of feeding, sepsis was induced by cecal ligation and puncture (CLP) and animals were monitored for survival. In a separate experiment, after 3 weeks of feeding mice underwent CLP and were sacrificed at various time points thereafter. Tissue was collected for biochemical studies. Mice fed a HFD gained more weight and had a greater fat mass compared to CD-fed mice. Mice on a HFD had a lower probability of survival and more severe lung injury compared with CD-fed mice following sepsis. Myeloperoxidase (MPO) activity, an indicator of neutrophil infiltration, was increased in the lung and liver after CLP in HFD-fed mice compared with CD (P < 0.05). The plasma cytokines tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were increased in both groups after CLP, however, TNF-α and IL-6 levels were lower in HFD mice at 3 h after CLP compared with CD and consistent with lung, but not liver, messenger RNA (mRNA) expression. Leptin levels were higher in HFD-fed mice at 18 h after sepsis compared to baseline levels (P < 0.05). Polymicrobial sepsis increased hepatic nuclear factor-κB (NF-κB) activation in HFD-fed mice after CLP vs. CD-fed mice. Short duration high fat feeding increases mortality and organ injury following polymicrobial sepsis. These effects correspond to changes in NF-κB.
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Jennifer.Kaplan@cchmc.org
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Kaplan
authors.forename: Marchele
authors.initials: M
authors.lastname: Nowell
authors.forename: Patrick
authors.initials: P
authors.lastname: Lahni
authors.forename: Michael P
authors.initials: MP
authors.lastname: O'Connor
authors.forename: Paul W
authors.initials: PW
authors.lastname: Hake
authors.forename: Basilia
authors.initials: B
authors.lastname: Zingarelli
mesh_terms: D000818:Animals; D002432:Cecum / Q000293:injuries / Q000473:pathology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008026:Ligation; D008099:Liver / Q000293:injuries / Q000473:pathology*; D008168:Lung / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000097:blood; D018805:Sepsis / Q000378:metabolism / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D020738:Leptin; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha