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Lipid-enriched enteral nutrition controls the inflammatory response in murine Gram-negative sepsis.
Crit Care Med. 2010 Oct; 38(10):1996-2002.CC

Abstract

OBJECTIVES

Controlling the inflammatory cascade during sepsis remains a major clinical challenge. Recently, it has become evident that the autonomic nervous system reduces inflammation through the vagus nerve. The current study investigates whether nutritional stimulation of the autonomic nervous system effectively attenuates the inflammatory response in murine Gram-negative sepsis.

DESIGN

Controlled in vivo and ex vivo experimental study.

SETTINGS

Research laboratory of a university hospital.

SUBJECTS

Male C57bl6 mice.

INTERVENTIONS

Mice were intraperitoneally challenged with lipopolysaccharide derived from Escherichia coli. Before lipopolysaccharide administration, mice were fasted or enterally fed either lipid-rich nutrition or low-lipid nutrition. Antagonists to cholecystokinin receptors or nicotinic receptors were administered before lipopolysaccharide administration. Blood and tissue samples were collected at 90 mins. Mesenteric afferent discharge was determined in ex vivo preparations in response to both nutritional compositions.

MEASUREMENTS AND MAIN RESULTS

Both lipid-rich and low-lipid nutrition dose-dependently reduced lipopolysaccharide-induced tumor necrosis factor-α release (high dose: both 1.4 ± 0.4 ng/mL) compared with fasted mice (3.7 ± 0.8 ng/mL; p < .01). The anti-inflammatory effect of both nutritional compositions was mediated through cholecystokinin receptors (p < .01), activation of mesenteric vagal afferents (p < .05), and peripheral nicotinic receptors (p < .05). Lipid-rich nutrition attenuated the inflammatory response at lower dosages than low-lipid nutrition, indicating that enrichment of enteral nutrition with lipid augments the anti-inflammatory potential. Administration of lipid-rich nutrition prevented endotoxin-induced small intestinal epithelium damage and reduced inflammation in the liver and spleen compared with fasted (all p < .01) and low-lipid nutrition controls (all p < .05).

CONCLUSIONS

The current study demonstrates that lipid-rich nutrition attenuates intestinal damage and systemic as well as organ-specific inflammation in murine Gram-negative sepsis through the nutritional vagal anti-inflammatory pathway. These findings implicate enteral administration of lipid-enriched nutrition as a promising intervention to modulate the inflammatory response during septic conditions.

Authors+Show Affiliations

Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20639744

Citation

Lubbers, Tim, et al. "Lipid-enriched Enteral Nutrition Controls the Inflammatory Response in Murine Gram-negative Sepsis." Critical Care Medicine, vol. 38, no. 10, 2010, pp. 1996-2002.
Lubbers T, De Haan JJ, Hadfoune M, et al. Lipid-enriched enteral nutrition controls the inflammatory response in murine Gram-negative sepsis. Crit Care Med. 2010;38(10):1996-2002.
Lubbers, T., De Haan, J. J., Hadfoune, M., Zhang, Y., Luyer, M. D., Grundy, D., Buurman, W. A., & Greve, J. W. (2010). Lipid-enriched enteral nutrition controls the inflammatory response in murine Gram-negative sepsis. Critical Care Medicine, 38(10), 1996-2002. https://doi.org/10.1097/CCM.0b013e3181eb90d7
Lubbers T, et al. Lipid-enriched Enteral Nutrition Controls the Inflammatory Response in Murine Gram-negative Sepsis. Crit Care Med. 2010;38(10):1996-2002. PubMed PMID: 20639744.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lipid-enriched enteral nutrition controls the inflammatory response in murine Gram-negative sepsis. AU - Lubbers,Tim, AU - De Haan,Jacco-Juri, AU - Hadfoune,M'Hamed, AU - Zhang,Yiren, AU - Luyer,Misha D, AU - Grundy,David, AU - Buurman,Wim A, AU - Greve,Jan Willem, PY - 2010/7/20/entrez PY - 2010/7/20/pubmed PY - 2010/10/12/medline SP - 1996 EP - 2002 JF - Critical care medicine JO - Crit Care Med VL - 38 IS - 10 N2 - OBJECTIVES: Controlling the inflammatory cascade during sepsis remains a major clinical challenge. Recently, it has become evident that the autonomic nervous system reduces inflammation through the vagus nerve. The current study investigates whether nutritional stimulation of the autonomic nervous system effectively attenuates the inflammatory response in murine Gram-negative sepsis. DESIGN: Controlled in vivo and ex vivo experimental study. SETTINGS: Research laboratory of a university hospital. SUBJECTS: Male C57bl6 mice. INTERVENTIONS: Mice were intraperitoneally challenged with lipopolysaccharide derived from Escherichia coli. Before lipopolysaccharide administration, mice were fasted or enterally fed either lipid-rich nutrition or low-lipid nutrition. Antagonists to cholecystokinin receptors or nicotinic receptors were administered before lipopolysaccharide administration. Blood and tissue samples were collected at 90 mins. Mesenteric afferent discharge was determined in ex vivo preparations in response to both nutritional compositions. MEASUREMENTS AND MAIN RESULTS: Both lipid-rich and low-lipid nutrition dose-dependently reduced lipopolysaccharide-induced tumor necrosis factor-α release (high dose: both 1.4 ± 0.4 ng/mL) compared with fasted mice (3.7 ± 0.8 ng/mL; p < .01). The anti-inflammatory effect of both nutritional compositions was mediated through cholecystokinin receptors (p < .01), activation of mesenteric vagal afferents (p < .05), and peripheral nicotinic receptors (p < .05). Lipid-rich nutrition attenuated the inflammatory response at lower dosages than low-lipid nutrition, indicating that enrichment of enteral nutrition with lipid augments the anti-inflammatory potential. Administration of lipid-rich nutrition prevented endotoxin-induced small intestinal epithelium damage and reduced inflammation in the liver and spleen compared with fasted (all p < .01) and low-lipid nutrition controls (all p < .05). CONCLUSIONS: The current study demonstrates that lipid-rich nutrition attenuates intestinal damage and systemic as well as organ-specific inflammation in murine Gram-negative sepsis through the nutritional vagal anti-inflammatory pathway. These findings implicate enteral administration of lipid-enriched nutrition as a promising intervention to modulate the inflammatory response during septic conditions. SN - 1530-0293 UR - https://www.unboundmedicine.com/medline/citation/20639744/Lipid_enriched_enteral_nutrition_controls_the_inflammatory_response_in_murine_Gram_negative_sepsis_ L2 - https://dx.doi.org/10.1097/CCM.0b013e3181eb90d7 DB - PRIME DP - Unbound Medicine ER -