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 six-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 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 (TNFα) and interleukin (IL)-6 were increased in both groups after CLP, however TNFα and IL-6 levels were lower in HFD mice at 3h after CLP compared with CD and consistent with lung, but not liver, mRNA expression. Leptin levels were higher in HFD-fed mice at 18h 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.

Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr−/− Mice

“…This is because LDLr 2/2 mice gain less weight and fat mass when fed a WHF diet compared with LDLr +/+ mice on the same background and are thus less prone to obesity and obesity-induced inflammation (45)(46)(47). Of interest, an acute dietary intervention of 1 wk did not alter the T cell response in CHS, likely because the lipid composition of T cells had not changed after 1 wk of WHF diet and/or owing to enhanced (polarized) innate inflammatory responses to the acute high-fat feeding (48), at the expense of a lower T cell response. LDLr 2/2 mice do not possess LDL receptors, and therefore liver and other cell types cannot remove cholesterol-rich intermediatedensity lipoproteins and LDLs from plasma, resulting in the buildup of circulating lipids (49,50).…”

The effects of LPS-induced endotoxemia on the expression of adiponectin and its receptors in female rats

“…Although it has been reported that APN plays pivotal roles in the regulation of acute inflammatory responses [8][9][10][11][12][13][14][15][16][17], the changes in the expression levels of endogenous APN and AdipoR during such conditions have not been fully elucidated, especially in females. Therefore, the present study mainly focused on the effects of LPS-induced sepsis on APN and AdipoR expression in peripheral and central tissues in female rats.…”

“…Although some studies have detected alterations in endogenous APN and AdipoR expression levels under septic conditions, the results of these studies are contradictory. For example, whilst some reports have shown that serum APN levels are decreased by LPS-or cecal ligation and puncture (CLP)-induced sepsis in WT mice and rats [10,11,18], another study found that the serum APN level was not affected by CLP-induced sepsis in WT mice [12]. In addition, the injection of a septic dose of LPS into lean male rats did not affect their visceral WAT APN mRNA expression.…”

“…On the other hand, increased serum APN levels are associated with mortality in patients that suffer respiratory failure [9]. In polymicrobial-or lipopolysaccharide (LPS)-induced septic conditions, APN knockout (KO) and obese APNdeficient rodents display significantly higher mortality rates than wild-type (WT) controls [10][11][12][13]. Similarly, it was found that polymicrobial-induced sepsis caused worse hepatic injuries in APN KO mice than in the WT serum, hepatic, and hypothalamic levels were also measured.…”

The obese child in the Intensive Care Unit. Update

“…98,99 However, there is cumulative evidence that obese patients are more prone to having severe complications from common infections. 100,101 In an experimental cecal ligation and puncture (CLP) model of sepsis in mice, diet was modified briefly to induce obesity and assess inflammatory response. The model demonstrated that mice had a lower chance of survival and greater organ damage, which was dependent on changes in nuclear factor-κB.…”