Lipid-rich enteral nutrition regulates mucosal mast cell activation via the vagal anti-inflammatory reflex.

Nutritional stimulation of the cholecystokinin-1 receptor (CCK-1R) and nicotinic acetylcholine receptor (nAChR)-mediated vagal reflex was shown to reduce inflammation and preserve intestinal integrity. Mast cells are important early effectors of the innate immune response; therefore modulation of mucosal mast cells is a potential therapeutic target to control the acute inflammatory response in the intestine. The present study investigates intestinal mast cell responsiveness upon nutritional activation of the vagal anti-inflammatory reflex during acute inflammation.

Cholecystokinin/Cholecystokinin-1 receptor-mediated peripheral activation of the afferent vagus by enteral nutrients attenuates inflammation in rats.

Objective: The current study investigates activation of the nutritional anti-inflammatory pathway by lipid-rich nutrition.

Background: Enteral nutrition activates humoral and neural pathways to regulate food intake and sustain energy balance. Recently, we demonstrated that enteral nutrition and in particular lipid-rich nutrition modulates inflammation and prevents organ damage.

Biodistribution and pharmacokinetics of PEG-10kDa-cholecystokinin-10 in rats after different routes of administration.

Cholecystokinin, produced in the proximal small intestine, is a short acting satiating peptide hormone. CCK-10, before and after mono-iodination, was previously coupled to 10kDa polyethylene glycol (PEG). The formed conjugates PEG10kDa-CCK-10 and PEG10kDa-[(127)I]-CCK-10 show after i.

Disruption of the behavioral satiety sequence by simmondsin.

Simmondsin, a cyanoglycoside from jojoba meal, reduces food intake after oral administration. To diagnose if it acts by inducing satiation or by creating abnormal physiological effects, an observational study was undertaken to investigate the effects of simmondsin on feeding and other behaviors. Particular attention was paid to the behavioral sequence associated with satiety (BSS).

Lack of tolerance development with long-term administration of PEGylated cholecystokinin.

Cholecystokinin (CCK) is a short acting satiating peptide hormone produced in the proximal small intestine. Daily CCK injection in rats initially inhibits food intake, but after several days, food intake is no longer affected, suggesting development of tolerance. Previously, we covalently coupled CCK to a 10kDa polyethylene glycol (mPEG-OH) and showed that this conjugate, PEG-CCK(9), produced a significantly longer anorectic effect than unmodified CCK(9).

PEGylation of cholecystokinin prolongs its anorectic effect in rats.

The anorectic compound CCK-9 was coupled to polyethylene glycol 5 kDa, 10 kDa, 20 kDa and 30 kDa, under different reaction conditions. Conjugates were purified by HPLC and characterized by MALDI-TOF MS. A 96% PEGylation yield was obtained in buffer pH 7.