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Lipid-enriched nutrition reduces inflammation via local activation of the autonomic nervous system by cholecystokinin


The present study investigates the nutritional activation of the cholinergic anti-inflammatory pathway. Lipid-enriched nutrition effectively attenuates systemic inflammation and prevents gut barrier failure by stimulation of the cholinergic pathway via cholecystokinin (CCK) receptors. This study investigates whether enteral lipids activate the autonomic nervous system via local stimulation of CCK receptors on the afferent vagus or by activation of receptors within the central nervous system via circulating CCK.


Sprague–Dawley rats were subjected to hemorrhagic shock. Before shock, animals were fasted or fed a lipid-enriched oral nutrition at 18 hours, 2 hours and 45 minutes. Peripheral activation of the autonomic nervous system was determined by performing deafferentations with perivagal application of capsaicin prior to shock. Central activation of the autonomic nervous system by circulating levels of CCK was studied by infusion of high levels of sulfated CCK8 starting 30 minutes prior to shock until sacrifice in fasted animals. Plasma and tissue samples were collected 90 minutes after shock to assess the inflammatory status and gut barrier function.


Deafferentation significantly abrogated the inhibitory effect of dietary fat on TNFα (133.7 ± 31.6 pg/ml vs 45.3 ± 12.9 pg/ml (sham); P < 0.001) and IL-6 (168 ± 14 pg/ml vs 69 ± 9 pg/ml (sham); P < 0.001). Preservation of gut barrier function was hindered by vagal deafferentation, expressed as increased leakage of HRP in ileal segments (6.1 ± 0.3 μg/ml vs 2.7 ± 0.3 μg/ml (sham); P < 0.001) and bacterial translocation (113 ± 20 CFU/g tissue vs 33 ± 4 CFU/g tissue (sham); P < 0.001). Infusion of sulfated CCK8 (arterial levels: 13 ± 2 pM at shock and 19 ± 4 pM at sacrifice) failed to attenuate inflammation and improve gut barrier function.


Our study shows for the first time that lipid-enriched nutrition attenuates systemic inflammation and improves intestinal integrity via local activation of the afferent vagus nerve. The presence of enteral lipids is essential to exert these protective effects. Clinically, nutritional activation of this potent anti-inflammatory pathway could provide a novel therapeutic treatment for patients prone to develop excessive inflammation.

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Lubbers, T., De Haan, J., Luyer, M. et al. Lipid-enriched nutrition reduces inflammation via local activation of the autonomic nervous system by cholecystokinin. Crit Care 12 (Suppl 2), P145 (2008).

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