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Short‐Term High Fat Feeding Increases Organ Injury and Mortality After Polymicrobial Sepsis
Author(s) -
Kaplan Jennifer M.,
Nowell Marchele,
Lahni Patrick,
O'Connor Michael P.,
Hake Paul W.,
Zingarelli Basilia
Publication year - 2012
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2012.40
Subject(s) - sepsis , medicine , tumor necrosis factor alpha , myeloperoxidase , endocrinology , lung , inflammation , leptin , obesity
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.