Gastric emptying changes are neither necessary nor sufficient for CCK-induced satiety

1989 ◽  
Vol 256 (1) ◽  
pp. R56-R62
Author(s):  
K. L. Conover ◽  
S. M. Collins ◽  
H. P. Weingarten
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Significant Role ◽  
Test Meal ◽  
Meal Size ◽  
High Dose ◽  
Reduce Food Intake ◽  
Cholecystokinin Octapeptide ◽  
No Inhibition

If gastric emptying plays a significant role in the satiety produced by exogenous cholecystokinin octapeptide (CCK-8) then 1) the effects on emptying and feeding should share similar kinetics and 2) peptides that inhibit emptying should also inhibit feeding. In the first experiment, CCK-8 (5.6 micrograms/kg) injected immediately before the introduction of an intragastric load (10 ml saline) or presentation of a test meal (15% sucrose) produced a rapid inhibition of both emptying and feeding. In contrast, the same dose administered 15 min before testing caused no inhibition of emptying, even though it retained the ability to reduce meal size. In experiment 2, the abilities of the peptides pentagastrin (100 micrograms/kg), bombesin (8 and 16 micrograms/kg), and secretin (2.86, 14.3, and 28.6 micrograms/kg) to reduce food intake and inhibit emptying were tested. Pentagastrin influenced neither food intake nor gastric emptying. Bombesin caused a small transient delay in emptying but a large and sustained eating suppression. However, a high dose of secretin caused no significant reduction of food intake, in spite of the fact that it inhibited emptying to the same degree as 1.4 micrograms/kg CCK-8, which does reduce intake. These results suggest that the inhibition of emptying by CCK is not sufficient to explain the satiety effect of CCK-8.

Infusion of CCK-8 into hepatic-portal vein fails to reduce food intake in rats

1987 ◽  
Vol 252 (5) ◽  
pp. R1015-R1018 ◽  
Author(s):  
D. Greenberg ◽  
G. P. Smith ◽  
J. Gibbs
Keyword(s):  
Food Intake ◽  
Portal Vein ◽  
Test Meal ◽  
Intraperitoneal Administration ◽  
Meal Size ◽  
Reduce Food Intake ◽  
Hormonal Mechanism ◽  
Hepatic Portal Vein ◽  
Hepatic Portal ◽  
Intraportal Infusion

If the putative satiating effect of endogenous cholecystokinin (CCK) is produced through a circulating hormonal mechanism, then administration of exogenous CCK into the hepatic-portal vein should decrease meal size. To test this, one form of endogenous CCK, the C-terminal octapeptide CCK-8, was infused intraportally in doses of 4 and 8 micrograms/kg just prior to a test meal. Neither dose decreased food intake after intraportal infusion even though intraperitoneal administration of 4 micrograms/kg CCK-8 decreased meal size approximately 50% in the same rats. The results suggest that if endogenous CCK-8 has a satiating effect, it acts primarily through a paracrine mechanism.

Effect of a soup preload on reduction of food intake by cholecystokinin in humans

1991 ◽  
Vol 260 (4) ◽  
pp. R672-R680 ◽  
Author(s):  
N. E. Muurahainen ◽  
H. R. Kissileff ◽  
J. Lachaussee ◽  
F. X. Pi-Sunyer
Keyword(s):  
Food Intake ◽  
Test Meal ◽  
Interactive Effect ◽  
The Other ◽  
Reduce Food Intake ◽  
Cholecystokinin Octapeptide ◽  
Meal Intake ◽  
Treatment Conditions

Cholecystokinin octapeptide (CCK-8) or saline was intravenously infused for 5 min before and 5 min during a meal of macaroni and beef, served 20 min after a preload of either 100 or 500 g of soup to 12 nonobese men. Intake of the test meal was significantly lower when CCK-8 was given, following the larger preload, than after any of the other treatments. There were no significant differences among the other three treatment conditions. These results are consistent with the hypothesis that gastric, but not merely pregastric, stimulation interacts with CCK-8 to reduce food intake in humans. Although gastric filling seems to be the most likely stimulus for the interactive effect with CCK-8, other factors such as activation of nutrient-sensitive sites cannot be eliminated. In addition, hunger ratings were significantly lower immediately after the larger soup preloads than after the smaller. Hunger ratings after the soup also correlated better with test-meal intake after the large soup preloads with and without CCK-8 than after the smaller preloads. Hunger did not correlate significantly with test meal intake after the small soup preload with CCK-8. These results suggest that hunger ratings are more sensitive predictors of intake when the stomach is relatively full (i.e., after a large preload) than when it is relatively empty (i.e., after a small preload) at the time the hunger rating is taken.

Cholecystokinin is a Satiety Hormone in Humans at Physiological Post-Prandial Plasma Concentrations

1995 ◽  
Vol 89 (4) ◽  
pp. 375-381 ◽  
Author(s):  
Anne Ballinger ◽  
Lorraine McLoughlin ◽  
Sami Medbak ◽  
Michael Clark
Keyword(s):  
Food Intake ◽  
Test Meal ◽  
Plasma Concentrations ◽  
Standard Test ◽  
Saline Infusion ◽  
Reduce Food Intake ◽  
Subsequent Test ◽  
Gut Hormone ◽  
Plasma Cholecystokinin ◽  
Satiety Hormone

1. Intravenous infusions of the brain/gut hormone, cholecystokinin, have been shown to reduce food intake in a subsequent test meal. However, in previous studies the doses administered were large and likely to have produced plasma concentrations far in excess of the normal post-prandial range. 2. In this study cholecystokinin-8 was infused intravenously to six healthy subjects in doses that reproduced physiological post-prandial concentrations. Plasma concentrations of cholecystokinin were measured using a novel sensitive and specific radioimmunoassay. The effect of cholecystokinin-8 infusion on subsequent food intake in a standard test meal was compared with the effect of saline infusion in the same subjects. 3. Food intake (mean ± SEM) was significantly less during cholecystokinin (5092 ± 665 kJ) than during saline infusion (6418 ± 723 kJ, P = 0.03). During cholecystokinin infusion, plasma concentrations increased from 0.45 ± 0.06 pmol/l to 7.28 ± 2.43 pmol/l immediately before the meal. With saline infusion there was no premeal increase in plasma cholecystokinin concentration. 4. This paper describes a novel radioimmunoassay for measurement of plasma concentrations of cholecystokinin. Using this assay we have demonstrated that cholecystokinin is important in control of satiety in humans.

Analyses of Gastric Emptying in Bluegill (Lepomis macrochirus)

1976 ◽  
Vol 33 (7) ◽  
pp. 1630-1633 ◽  
Author(s):  
F. M. El-Shamy
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Multiple Regression ◽  
Statistical Models ◽  
Lepomis Macrochirus ◽  
Meal Size ◽  
Equivalent Amount ◽  
Single Meal ◽  
Time Of Feeding

Bluegill (Lepomis macrochirus) fed a single meal averaging 111.6 mg dry wt (2.19% body wt on a wet fish and food basis) showed an average of 60 mg (54%) of the meal remaining after 8 h of digestion compared to 71 mg (59%) of an equivalent amount of food (119.6 mg or 2.04% body wt) fed in two consecutive meals. Fish fed a single meal averaging 167.2 mg (2.74% body wt) showed an average of 41% of the meal remaining 12 h after feeding, while fish fed three consecutive meals totaling 140.3 mg (2.51% body wt), showed an average of 47% of the food intake remaining 12 h after they were first fed. Two statistical models — an exponential and a multiple regression — relating food digested to meal size and time of feeding were developed. Both statistical models, when based on results of fish fed single meals, failed to predict values comparable to those observed for bluegill fed multiple meals.

Cholecystokinin Octapeptide Action on Gastric Emptying and Food Intake in Normal and Vagotomized Man

1985 ◽  
Vol 448 (1) ◽  
pp. 640-641 ◽  
Author(s):  
M. J. SHAW ◽  
J. J. HUGHES ◽  
J. E. MORLEY ◽  
A. S. LEVINE ◽  
S. E. SILVIS ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Cholecystokinin Octapeptide

Endogenous and exogenous cholecystokinin may reduce food intake by different mechanisms

1987 ◽  
Vol 253 (2) ◽  
pp. R379-R382
Author(s):  
G. Shillabeer ◽  
J. S. Davison
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Intraperitoneal Injection ◽  
Motor Pattern ◽  
Reduce Food Intake ◽  
Motor Responses ◽  
Decrease Food Intake ◽  
Gastric Pressure ◽  
Gastrointestinal Motor

To determine whether exogenous cholecystokinin (CCK) and endogenous CCK evoke different gastrointestinal motor responses, we investigated the motility induced by CCK by use of standard manometric methods. Injection (ip) of 500 ng/kg CCK caused immediate profound gastric inhibition and duodenal phasic excitation that did not resemble the postprandial pattern. Similar profound gastric inhibition has been associated with nausea. The contribution of endogenous CCK to the fed pattern of motility was investigated using proglumide; intraperitoneal injection of the antagonist before feeding caused no change, but injection before a second meal induced a decrease (P less than 0.025, n = 6) in gastric pressure with no accompanying duodenal change. This suggests that CCK causes an increase in gastric pressure that could result from a delay in gastric emptying. In support of this hypothesis, we have previously demonstrated, by use of proglumide, that endogenous CCK delays gastric emptying. Therefore exogenous CCK may reduce food intake by evoking an abnormal gastrointestinal motor pattern that may induce malaise, whereas endogenous CCK may decrease food intake by delaying gastric emptying, thus prolonging gastric satiety signals.

NMDA receptor participation in control of food intake by the stomach

2000 ◽  
Vol 278 (5) ◽  
pp. R1362-R1368 ◽  
Author(s):  
Mihai Covasa ◽  
Robert C. Ritter ◽  
Gilbert A. Burns
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Nmda Receptors ◽  
Nmda Antagonist ◽  
Meal Size ◽  
Sham Feeding ◽  
Gastric Emptying Rate ◽  
Mk 801 ◽  
Direct Measurements ◽  
Increase Food Intake

We previously reported that MK-801 (dizocilpine), an antagonist of N-methyl-d-aspartate (NMDA)-type glutamate receptors, increased meal size and duration in rats. MK-801 did not increase sham feeding or attenuate reduction of sham feeding by intraintestinal nutrient infusions. These results suggested that the MK-801-induced increase in meal size did not depend on antagonism of postgastric satiety signals. Consequently, we hypothesized that the NMDA antagonist might increase food intake by directly antagonizing gastric mechanosensory signals or by accelerating gastric emptying, thereby reducing gastric mechanoreceptive feedback. To test this hypothesis, we recorded intake of 15% sucrose in rats implanted with pyloric cuffs that could be closed to prevent gastric emptying. Sucrose intake was increased when the pyloric cuffs were open, allowing the stomach to empty. However, intake was not increased when the pyloric cuffs were inflated, causing gastric retention of all ingested sucrose. Direct measurements of gastric emptying revealed that MK-801 accelerated the emptying of 5-ml loads of 0.9% NaCl and 15% sucrose. Furthermore, MK-801 also accelerated the rate of emptying of freely ingested sucrose regardless of the volume ingested. Taken together with our previous findings, these results indicate that blockade of NMDA receptors with MK-801 does not increase food intake by antagonizing gastric mechanosensation. Rather, it accelerates gastric emptying, and thereby may indirectly reduce gastric mechanoreceptive cues, resulting in prolongation of eating. Modulation of gastric emptying rate by NMDA receptors could play an important role in the control of meal sizes.

scholarly journals Central Nesfatin-1 Reduces Dark-Phase Food Intake and Gastric Emptying in Rats: Differential Role of Corticotropin-Releasing Factor2 Receptor

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 4911-4919 ◽  
Author(s):  
Andreas Stengel ◽  
Miriam Goebel ◽  
Lixin Wang ◽  
Jean Rivier ◽  
Peter Kobelt ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Hypothalamic Nucleus ◽  
Reduce Food Intake ◽  
Dark Phase ◽  
Crf2 Receptor ◽  
Brain Ventricle ◽  
Dose Dependent

Nesfatin-1, derived from nucleobindin2, is expressed in the hypothalamus and reported in one study to reduce food intake (FI) in rats. To characterize the central anorexigenic action of nesfatin-1 and whether gastric emptying (GE) is altered, we injected nesfatin-1 into the lateral brain ventricle (intracerebroventricular, icv) or fourth ventricle (4v) in chronically cannulated rats or into the cisterna magna (intracisternal, ic) under short anesthesia and compared with ip injection. Nesfatin-1 (0.05 μg/rat, icv) decreased 2–3 h and 3–6 h dark-phase FI by 87 and 45%, respectively, whereas ip administration (2 μg/rat) had no effect. The corticotropin-releasing factor (CRF)1/CRF2 antagonist astressin-B or the CRF2 antagonist astressin2-B abolished icv nesfatin-1’s anorexigenic action, whereas an astressin2-B analog, devoid of CRF-receptor binding affinity, did not. Nesfatin-1 icv induced a dose-dependent reduction of GE by 26 and 43% that was not modified by icv astressin2-B. Nesfatin-1 into the 4v (0.05 μg/rat) or ic (0.5 μg/rat) decreased cumulative dark-phase FI by 29 and 60% at 1 h and by 41 and 37% between 3 and 5 h, respectively. This effect was neither altered by ic astressin2-B nor associated with changes in GE. Cholecystokinin (ip) induced Fos expression in 43% of nesfatin-1 neurons in the paraventricular hypothalamic nucleus and 24% of those in the nucleus tractus solitarius. These data indicate that nesfatin-1 acts centrally to reduce dark phase FI through CRF2-receptor-dependent pathways after forebrain injection and CRF2-receptor-independent pathways after hindbrain injection. Activation of nesfatin-1 neurons by cholecystokinin at sites regulating food intake may suggest a role in gut peptide satiation effect.

The GLP-1 agonist exendin-4 reduces food intake in nonhuman primates through changes in meal size

2007 ◽  
Vol 293 (3) ◽  
pp. R983-R987 ◽  
Author(s):  
Karen A. Scott ◽  
Timothy H. Moran
Keyword(s):  
Food Intake ◽  
Rhesus Macaques ◽  
Specific Effect ◽  
Meal Size ◽  
Reduce Food Intake ◽  
Dependent Manner ◽  
Primate Model ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Dose Dependent

Exendin-4 (Ex4), a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and suppress gastric emptying in rodents and humans. In this study we investigated the effects of peripheral administration of Ex4 on food intake and meal patterns in adult male rhesus macaques. Rhesus macaques ( n = 4) that had been trained to lever press for food pellets were injected intramuscularly 15 min before the start of their 6-h daily feeding period. Ex4 was given at doses of 0.10, 0.32, 0.56, 1.0, and 3.0 μg/kg. Ex4 suppressed food intake in a dose-dependent manner, with the 3.0 μg/kg dose completely preventing feeding during the 6-h period and the 0.10 μg/kg dose suppressing intake by 17%. Doses of 0.32, 0.56, 1.0, and 3.0 μg/kg caused significant reductions in cumulative intake at all six hourly time points. Ex4 inhibited food intake through a specific effect on meal size. Meal size was significantly reduced in a dose-dependent manner with significant reductions at the 0.32 and 1.0 μg/kg doses ( P < 0.05). Day 2 and 3intakes returned to baseline levels with no compensation for Ex4-induced feeding suppression. Administration of doses of 0.32 and 0.56 μg/kg Ex4 over 5 consecutive days led to sustained reductions in intake with no evidence of compensation. Again, these reductions were due to specific effects on meal size. These results demonstrate that activation of GLP-1 pathways has potent effects on the controls of meal size and overall food intake in a nonhuman primate model.

Lesions of area postrema attenuate but do not prevent anorectic action of peripheral serotonin in rats

1995 ◽  
Vol 269 (6) ◽  
pp. R1314-R1320 ◽  
Author(s):  
V. Adipudi ◽  
K. J. Simansky
Keyword(s):  
Food Intake ◽  
Dose Response ◽  
Area Postrema ◽  
Behavioral Analysis ◽  
High Dose ◽  
Reduce Food Intake ◽  
Circumventricular Organ ◽  
Behavioral Toxicity ◽  
Dose Dependent ◽  
Dose Response Function

These studies assessed the effect of selectively ablating the area postrema (AP) on the action of peripheral serotonin [5-hydroxytryptamine (5-HT)] to reduce food intake in rats. Intraperitoneal 5-HT (0, 2.0, 4.0, and 8.0 mumol/kg) reduced the intakes of sweetened mash during a 30-min test in controls (APC) and in AP-lesioned rats (APX). The anorexia was dose dependent in controls but the dose-response function was flat after AP lesions. In another study, 2.0 mumol/kg 5-HT reduced intakes of both groups by approximately 25%, but AP lesions blunted the effect at 8.0 mumol/kg 5-HT (APX, -30% vs. APC, -85%). Behavioral analysis revealed that, compared with controls, AP lesions eliminated the decrease in frequency of feeding and reduced the incidence of resting and of an aberrant posture observed after 8.0 mumol/kg. Thus peripheral 5-HT decreases food intake in rats with AP lesions. Multiple mechanisms appear to be involved in the ability of peripheral 5-HT to reduce feeding. A high dose of 5-HT promotes responses associated with satiation but also produces behavioral toxicity; these effects involve the AP. Lower doses appear to engage processes that do not rely on the function of this circumventricular organ.

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