These data demonstrate that enteral lipid-rich nutrition modulates inflammation and preserves intestinal integrity via CCK release which activates CCK-1 receptors located on afferent vagal fibers. Taken together, the current study reveals a novel gut-brain-immune axis and provides new insight into the applicability of enteral nutrition to treat inflammatory conditions.

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. Mucosal mast cell degranulation was induced in C57/Bl6 mice by administration of Salmonella enterica LPS. Lipid-rich enteral feeding prior to LPS significantly decreased circulatory levels of mouse mast cell protease at 30 min post-LPS compared with isocaloric low-lipid nutrition or fasting. CCK-1R blockage reversed the inhibitory effects of lipid-rich feeding, whereas stimulation of the peripheral CCK-1R mimicked nutritional mast cell inhibition. The effects of lipid-rich nutrition were negated by nAChR blockers chlorisondamine and α-bungarotoxin and vagal intestinal denervation. Accordingly, release of β-hexosaminidase by MC/9 mast cells following LPS or IgE-ovalbumin complexes was dose dependently inhibited by acetylcholine and nicotine. Application of GSK1345038A, a specific agonist of the nAChR α7, in bone marrow-derived mast cells from nAChR β2-/- and wild types indicated that cholinergic inhibition of mast cells is mediated by the nAChR α7 and is independent of the nAChR β2. Together, the present study reveals mucosal mast cells as a previously unknown target of the nutritional anti-inflammatory vagal reflex.

The aim of this study was to investigate the influence of isoenergetic substitution between the three energy delivering macronutrients in pre-starter diets on performance and intermediary nutrient metabolism in broiler chickens. From hatch until 5 days of age, 600 chicks, collected during peak of hatch, were fed one of the three experimental pre-starter diets with isoenergetic (13 MJ metabolisable energy/kg) substitutions between fat (43 vs. 108 g/kg), protein (126 vs. 240 g/kg) and carbohydrates (391 vs. 510 g/kg). After 5 days, commercial grower and finisher diets were provided. Pre-starter composition influenced body weight until slaughter age, although not statistically verifiable. Broilers fed the low protein (LP) pre-starter had the lowest body weight in relation to chickens on the low carbohydrate or low fat pre-starter diet. After hatch, chicks on the LP pre-starter diet were able to use the residual yolk sac more rapidly to fulfil their protein requirement, which is reflected in small intestine and liver development. Also, plasma metabolite levels were influenced mostly by the LP pre-starter, indicating that the main focus for the requirements of newly hatched chicks should be on proteins. Furthermore, optimal nutrition during the first day's post-hatch should take into account the contribution of the yolk.

Background and purpose: Acute intraperitoneal (i.p.) administration of cholecystokinin (CCK) is known to induce a significant, but short-lasting, reduction in food intake, followed by recovery within hours. Therefore, we had covalently coupled CCK to a 10 kDa polyethylene glycol and showed that this conjugate, PEG-CCK 9 , produced a significantly longer anorectic effect than unmodified CCK 9 . The present study assessed the dose-dependency of this response and the effect of two selective CCK 1 receptor antagonists, with different abilities to cross the blood-brain barrier (BBB), on PEG-CCK 9 -induced anorexia. Experimental approach: Food intake was measured, for up to 23 h, after i.p. administration of different doses (2, 4, 8, 16 and 32 mg kg À1 ) of CCK 9 or PEG-CCK 9 in male Wistar rats. Devazepide (100 mg kg À1 ), which penetrates the BBB or 2-NAP (3 mg kg À1 ), which does not cross the BBB, were coadministered i.p. with PEG-CCK 9 (6 mg kg À1 ) and food intake was monitored. Key results: In PEG-CCK 9 -treated rats, a clear dose-dependency was seen for both the duration and initial intensity of the anorexia whereas, for CCK 9 , only the initial intensity was dose-dependent. Intraperitoneal administration of devazepide or 2-NAP, injected immediately prior to PEG-CCK 9 , completely abolished the anorectic effect of PEG-CCK 9 . Conclusions and implications: The duration of the anorexia for PEG-CCK 9 was dose-dependent, suggesting that PEGylation of CCK 9 increases its circulation time. Both devazepide and 2-NAP completely abolished the anorectic effect of i.p. PEG-CCK 9 indicating that its anorectic effect was solely due to stimulation of peripheral CCK 1 receptors.

No abstract

Verbaeys I, Tolle V, Swennen Q, Zizzari P, Buyse J, Epelbaum J, Cokelaere M. Scheduled feeding results in adipogenesis and increased acylated ghrelin. Am J Physiol Endocrinol Metab 300: E1103-E1111, 2011. First published March 22, 2011; doi:10.1152/ajpendo.00551.2010.-Ghrelin, known to stimulate adipogenesis, displays an endogenous secretory rhythmicity closely related to meal patterns. Therefore, a chronic imposed feeding schedule might induce modified ghrelin levels and consequently adiposity. Growing Wistar rats were schedule-fed by imposing a particular fixed feeding schedule of 3 meals/day without caloric restriction compared with total daily control intake. After 14 days, their body composition was measured by DEXA and compared with ad libitum-fed controls and to rats daily intraperitoneal injection with ghrelin. Feeding patterns, circadian activity, and pulsatile acylated ghrelin variations were monitored. After 14 days, rats on the imposed feeding schedule displayed, despite an equal daily calorie intake, a slower growth rate compared with ad libitum-fed controls. Moreover, schedule-fed rats exhibiting a feeding pattern with intermittent fasting periods had a higher fat/lean ratio compared with ad libitum-fed controls. Interestingly, ghrelin-treated rats also showed an increase in fat mass, but the fat/lean ratio was not significantly increased compared with controls. In the schedule-fed rats, spontaneous activity and acylated ghrelin levels were increased and associated with the scheduled meals, indicating anticipatory effects. Our results suggest that scheduled feeding, associated with intermittent fasting periods, even without nutrient/ calorie restriction on a daily basis, results in adipogenesis. This repartitioning effect is associated with increased endogenous acylated ghrelin levels. This schedule-fed model points out the delicate role of meal frequency in adipogenesis and provides an investigative tool to clarify any effects of endogenous ghrelin without the need for ghrelin administration. metabolism; obesity; feeding patterns; meal frequency; dual-energy X-ray absorptiometry IN HUMANS, THE CORRELATION between meal patterns and obesity was pointed out in 1964, when Fábry et al. (19) reported that individuals consuming three meals or less per day were more overweight and more prone to hyperinsulinemia and glucose intolerance than those consuming five or more meals a day. Later on, an inverse relationship was shown between meal frequency and BMI in some (39) but not all populations studied (5, 18). Limited scientific literature on scheduled feeding, some going back more than 50 years, showed that force-fed rats also display a completely different metabolism with a concomitant change in body composition compared with freely fed rats despite similar caloric intake (2, 4, 10, 11).Previous research investigating the characteristics of a newly synthesized anorectic peptide, polyethylene glycol-cholecystokinin 9 (PEG-CCK 9 ) (28, 48 -50), revealed that rats fed a scheduled feeding to mimic the 3-to 6...

No abstract

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). The present study examined whether tolerance to the anorectic effect develops during long-term administration of PEG-CCK(9). For 14 consecutive days, male Wistar rats (n=12) received a daily i.p injection of 8microgkg(-1) of PEG-CCK(9) and a control group received a daily control injection of mPEG-OH. Body weight and food intake were monitored daily during the experiment. Effects on the pancreas were investigated. On each day, injection of PEG-CCK(9) induced an anorectic effect lasting 3-6h, but failed to significantly reduce daily total food intake compared to controls. The body weight gain of the PEG-CCK(9)-treated animals was not different from controls. The PEG-CCK(9)-treated group had a significantly higher pancreas weight, mainly due to hyperplasia. In conclusion, PEG-CCK(9) continued to have a daily suppressive effect on food intake when administered for 14 consecutive days, showing there was no development of tolerance.