title: Pretreatment with high-fat enteral nutrition reduces endotoxin and tumor necrosis factor-alpha and preserves gut barrier function early after hemorrhagic shock.
abstract: Gram-negative sepsis is a potentially fatal clinical syndrome characterized by a proinflammatory response (tumor necrosis factor-alpha) to bacterial (endo)toxins and gut barrier function loss. Recently, we found that high-fat enteral nutrition protects against late bacterial translocation in a model of hemorrhagic shock in rats. However, the basis for this protection is unknown. We hypothesized that the observed protection is the result of an early inhibition of endotoxin and the subsequent inflammatory response resulting in a preserved gut barrier function. Sprague-Dawley rats were divided into a group that was starved overnight (HS-S), fed with a low-fat enteral diet (HS-LF) or fed wih a high-fat enteral diet (HS-HF), and subsequently subjected to a nonlethal hemorrhagic shock. Ninety minutes after hemorrhage, arterial endotoxin significantly decreased in HS-HF rats (4.0 +/- 0.6 pg/mL) compared with HS-LF rats (10.7 +/- 0.9 pg/mL, P = 0.002) and HS-S rats (15.2 +/- 2.2 pg/mL P = 0.001). Interestingly, arterial tumor necrosis factor-alpha was also decreased in HS-HF rats (17.9 +/- 10.4 pg/mL) compared with HS-LF (83.5 +/- 16.7 pg/mL, P < 0.01) and HS-S rats (180.9 +/- 67.9 pg/mL, P < 0.02). Loss of tight junction structure (ZO-1) observed in ileum and colon of control hemorrhagic shock rats was prevented in HS-HF rats. In parallel, intestinal barrier function was preserved in HS-HF rats, evidenced by a reduced permeability to horseradish peroxidase (P < 0.05), less bacterial invasion, and a 10-fold reduction of bacterial translocation early after hemorrhagic shock. This report describes a new strategy to nutritionally prevent endotoxemia, the subsequent inflammatory response and gut barrier failure following hemorrhagic shock. High-fat enteral nutrition requires further evaluation as an intervention to prevent a potentially fatal systemic inflammatory response in patients at risk for sepsis.
authors.affiliation: Department of Surgery, Nutrition and Toxicology Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Misha D P
authors.initials: MD
authors.lastname: Luyer
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.forename: M'hamed
authors.initials: M
authors.lastname: Hadfoune
authors.forename: Jan A
authors.initials: JA
authors.lastname: Jacobs
authors.forename: Sergey R
authors.initials: SR
authors.lastname: Konstantinov
authors.forename: Cornelis H C
authors.initials: CH
authors.lastname: Dejong
authors.forename: Jan Willem M
authors.initials: JW
authors.lastname: Greve
mesh_terms: D000821:Animal Feed; D000818:Animals; D001158:Arteries / Q000473:pathology; D003106:Colon / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D004731:Endotoxins / Q000378:metabolism*; D004750:Enteral Nutrition; D005508:Food Deprivation; D007082:Ileum / Q000378:metabolism / Q000382:microbiology; D017404:In Situ Hybridization, Fluorescence; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis; D012769:Shock; D012771:Shock, Hemorrhagic / Q000473:pathology*; D019108:Tight Junctions; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
chemical_list: D004041:Dietary Fats; D004731:Endotoxins; D015850:Interleukin-6; D008074:Lipoproteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein