Cholecystokinin and stomach distension combine to reduce food intake in humans

2003 ◽  
Vol 285 (5) ◽  
pp. R992-R998 ◽  
Author(s):  
Harry R. Kissileff ◽  
Julie C. Carretta ◽  
Allan Geliebter ◽  
F. Xavier Pi-Sunyer
Keyword(s):  
Food Intake ◽  
Intravenous Infusion ◽  
Low Dose ◽  
Normal Weight ◽  
Saline Infusion ◽  
Gastric Distension ◽  
Reduce Food Intake ◽  
Gastric Balloon ◽  
Men And Women ◽  
Liquid Meal

The aim of this study was to test the hypothesis that gastric distension can enhance the effect of cholecystokinin (CCK) on reduction of food intake in men and women. Eight normal-weight subjects of each gender were tested four times each with either CCK or saline infusion crossed with gastric distension or no distension. Intravenous infusion of a low dose of CCK octapeptide (CCK-8; 112 ng/min for 23 min) combined with a subthreshold gastric distension induced by a water-filled balloon (300 ml) resulted in a significant (means ± SED: 191 ± 61 g in men, 209 ± 61 g in women, and 200 ± 43 g combined) reduction in intake of a liquid meal compared with saline infusion and unfilled gastric balloon. This combined effect was the result of a large and significant CCK effect when the stomach was distended (CCK vs. saline with distension: 169 ± 43 g) and a small and insignificant distension effect (distension vs. no distension without CCK: 31 ± 43 g). The CCK effect alone on intake (CCK vs. saline) without distension was not significant in men (72 ± 61 g) but was significant in women (121 ± 61 g). These results are consistent with the hypothesis that CCK's suppression of food intake is enhanced when the stomach is distended.

scholarly journals Combined effects of cholecystokinin-8 and gastric distension on food intake in humans

2019 ◽  
Vol 317 (1) ◽  
pp. R39-R48
Author(s):  
Harry R. Kissileff ◽  
Rebecca J. Gordon ◽  
John C. Thornton ◽  
Blandine Laferrère ◽  
Jeanine Albu ◽  
...  
Keyword(s):  
Food Intake ◽  
Interactive Effect ◽  
Normal Weight ◽  
Combined Effect ◽  
Gastric Distension ◽  
Reduce Food Intake ◽  
Additive Interaction ◽  
Physiol Regul Integr Comp ◽  
Human Participants ◽  
Healthy Participants

In a previous study (Kissileff HR, Carretta JC, Geliebter A, Pi-Sunyer FX. Am J Physiol Regul Integr Comp Physiol 285: R992–R998, 2003), when subthreshold gastric distension (300 ml) and a low dose of cholecystokinin octapeptide (CCK-8) (112 ng/min for 21 min) were concurrently administered to human participants, intake of a test meal was significantly reduced. However, the supra-additive interaction of CCK-8 and gastric distension was not significant. The purpose of the present study was to determine whether a significant interaction would be obtained when CCK-8 and gastric distension were each increased by 50% above levels used in the previous study. Twelve normal-weight, healthy participants were tested four times each with either CCK-8 (168 ng/min for 30 min) or saline infusion crossed with gastric distension (450 ml) or no distension. The combination of CCK-8 and gastric distension reduced food intake by a mean of 405 ± 86 g (SE) in comparison with the saline nondistension condition ( P < 0.001), which is a 51% reduction. Although there were some differences in the protocols, the combined effect was double that seen in the previous study. Although the interactive effect was larger [118 ± 109 g (SE)] than it was previously [73 ± 86 (SE)], it was not significant ( P = 0.29). There were also reports of a short-lived sick feeling after CCK-8, with and without distension, that was not observed in the previous study. Thus the combination of CCK-8 at 1.5 times threshold and gastric distension at 450 ml (increased from 300 ml) resulted in a combined effect to reduce food intake, which was also 1.5 times its previous value, and thus appears linear.

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.

scholarly journals Leptin and the Control of Food Intake: Neurons in the Nucleus of the Solitary Tract Are Activated by Both Gastric Distension and Leptin

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2189-2197 ◽  
Author(s):  
Lihong Huo ◽  
Lisa Maeng ◽  
Christian Bjørbæk ◽  
Harvey J. Grill
Keyword(s):  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Significant Proportion ◽  
Gastric Distension ◽  
Reduce Food Intake ◽  
Signal Transducer ◽  
Electrophysiological Response ◽  
Fluorescent Immunohistochemistry ◽  
Transcription 3

Leptin reduces food intake by an unspecified mechanism. Studies show that forebrain ventricular leptin delivery increases the inhibitory effects of gastrointestinal (GI) stimulation on intake and amplifies the electrophysiological response to gastric distension in neurons of the medial subnucleus of the nucleus tractus solitarius (mNTS). However, forebrain ventricular delivery leaves unspecified the neuroanatomical site(s) mediating leptin’s effect on intake. Detailed anatomical analysis in rats and mice by phosphorylated signal transducer and activator of transcription 3 immunohistochemistry shows that hindbrain leptin-responsive neurons are located exclusively within the mNTS. Here, we investigate 1) whether leptin and gastric distension affect the same mNTS neurons and 2) whether the intake-inhibitory action of gastric distension is potentiated by hindbrain leptin delivery. Twenty-five minutes after gastric balloon distension or sham distension, rats were injected with leptin or vehicle and killed 35 min later. Double-fluorescent immunohistochemistry for phosphorylated signal transducer and activator of transcription 3 and c-Fos revealed that about 40% of leptin-responsive cells also respond to gastric distension. A paradigm was then developed to examine the relationship between leptin and gastric distension volume on intake inhibition. At subthreshold levels, hindbrain ventricular leptin or distension volume were without effect. When combined, an interaction occurred that significantly reduced food intake. We conclude that 1) leptin-responsive neurons in the hindbrain are primarily located in the mNTS at the level of the area postrema, a key vagal afferent projection zone of the GI system; 2) a significant proportion of leptin-responsive neurons in the mNTS are activated by stomach distension; and 3) leptin delivered to the hindbrain is sufficient to potentiate the intake-suppressive effects of an otherwise ineffective volume of gastric distension. These results are consistent with the hypothesis that leptin acts directly on neurons within the mNTS to reduce food intake through an interaction with GI signal processing.

scholarly journals Water Drinking Induces Thermogenesis through Osmosensitive Mechanisms

2007 ◽  
Vol 92 (8) ◽  
pp. 3334-3337 ◽  
Author(s):  
Michael Boschmann ◽  
Jochen Steiniger ◽  
Gabriele Franke ◽  
Andreas L. Birkenfeld ◽  
Friedrich C. Luft ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Healthy Subjects ◽  
Crossover Trial ◽  
Normal Weight ◽  
Gastric Distension ◽  
Men And Women ◽  
Water Drinking ◽  
Randomized Controlled ◽  
Response To Water ◽  
Thermogenic Response

Abstract Context: Recently, we showed that drinking 500 ml water induces thermogenesis in normal-weight men and women. Objective: We now repeated these studies in a randomized, controlled, crossover trial in overweight or obese otherwise healthy subjects (eight men and eight women), comparing also the effects of 500 ml isoosmotic saline or 50 ml water. Results: Only 500 ml water increased energy expenditure by 24% over the course of 60 min after ingestion, whereas isoosmotic saline and 50 ml water had no effect. Heart rate and blood pressure did not change in these young, healthy subjects. Conclusions: Our data exclude volume-related effects or gastric distension as the mediator of the thermogenic response to water drinking. Instead, we hypothesize the existence of a portal osmoreceptor, most likely an ion channel.

Effects of pancreatic polypeptide, caerulein, and bombesin on satiety in obese mice

1985 ◽  
Vol 248 (3) ◽  
pp. G277-G280 ◽  
Author(s):  
I. L. Taylor ◽  
R. Garcia
Keyword(s):  
Food Intake ◽  
Pancreatic Polypeptide ◽  
Intraperitoneal Injection ◽  
Reduce Food Intake ◽  
Obese Mice ◽  
Liquid Meal ◽  
Bovine Pancreatic Polypeptide ◽  
Obesity Syndrome

Congenitally obese mice are hyperphagic, suggesting that their obesity is secondary to defects in normal satiety mechanisms. The present study compares the effects of caerulein, bombesin, and pancreatic polypeptide (three equimolar doses each of 3, 9, and 27 nmol/kg) on food intake in 10 pairs of lean and obese mice. After the intraperitoneal injection of saline, obese mice eat 240% more of a liquid meal (Magnacal) than their lean littermates (P less than 0.01). All three doses of caerulein significantly inhibited food intake in both obese and lean mice. Although the highest dose of bombesin significantly decreased food intake in both obese and lean mice, the lowest dose was only effective in obese mice. In contrast, none of these doses of pancreatic polypeptide had a significant effect on food intake in either lean or obese mice. A dose of bovine pancreatic polypeptide of 200 nmol/kg was required to significantly reduce food intake in lean and obese mice. This study demonstrates that obese mice respond to satiety signals and may even be more sensitive than their lean littermates to some messengers. In addition, the previously described reversal of this obesity syndrome by pancreatic polypeptide in doses of approximately 2.5 and 25 nmol X kg-1 X day-1 is unlikely to be due to effects of this peptide on food intake.

Overweight and obese boys reduce food intake in response to a glucose drink but fail to increase intake in response to exercise of short duration

2012 ◽  
Vol 37 (3) ◽  
pp. 520-529 ◽  
Author(s):  
Shlomi Tamam ◽  
Nick Bellissimo ◽  
Barkha P. Patel ◽  
Scott G. Thomas ◽  
G. Harvey Anderson
Keyword(s):  
Food Intake ◽  
Short Duration ◽  
Random Order ◽  
Normal Weight ◽  
Reduce Food Intake ◽  
Short Term ◽  
Total Food ◽  
Ad Libitum ◽  
Response To Exercise ◽  
Intake Regulation

The effect of short duration exercise (EXR) on food intake (FI) and energy balance (EB) is not well understood in either normal weight (NW) or overweight (OW) and obese (OB) 9–14 years old children. Our purpose was to describe the effects of activity and a glucose drink on short term FI, appetite, and EB in NW, OW, and OB boys. Each boy received in random order either a noncaloric Sucralose sweetened control or glucose (1.0 g·kg–1 body weight) drink 5 min after either exercise (EXR) or sedentary (SED) activity. Boys exercised for 15 min at their ventilation threshold (VT) in experiment 1 or at 25% above their VT in experiment 2. FI was measured at an ad libitum pizza meal 30 min after drink consumption. FI was lower after the glucose drink (p < 0.001) but not affected by activity, even though EXR increased appetite (p < 0.001). OW/OB boys ate more total food than NW boys (p = 0.020). EB over the duration of the experiments was reduced by EXR in OW/OB boys (p = 0.013) but not in NW boys in either experiment (p > 0.05). We conclude that intake regulation in OW/OB boys in response to a glucose drink is similar to NW boys, but it may be less responsive to activity.

scholarly journals Exiguous premeal saccharide intake reduces subsequent food intake in men

2021 ◽  
Author(s):  
Juliane Richter ◽  
Narona Thordsen ◽  
Kai Duysen ◽  
Kerstin M. Oltmanns
Keyword(s):  
Food Intake ◽  
Serum Insulin ◽  
Energy Levels ◽  
Caloric Intake ◽  
Body Weight Loss ◽  
Primary Energy ◽  
Normal Weight ◽  
Reduce Food Intake ◽  
Low Calorie ◽  
Calorie Consumption

Abstract Purpose Satiety is a crucial factor in the attempt to reduce food intake for long-term body weight loss. Since there is evidence for a negative correlation between cerebral energy levels and food intake, the provision of the primary energy substrate glucose to the brain through oral ingestion of carbohydrates could trigger feelings of satiety. Therefore, we hypothesized that a low-calorie saccharide preload would increase satiety, reduce subsequent food intake, and thereby decrease overall calorie consumption. Methods In a randomized single-blind crossover study, 17 healthy young normal-weight men received saccharide (26 kcal in total) or placebo capsules 30 min before a standardized breakfast buffet. We analysed food intake from the test buffet as well as plasma glucose and serum insulin levels. Results The saccharide preload reduced food intake from the buffet by 168 (± 34) kcal (p < 0.001) compared to control. This corresponds to a net reduction in total calorie consumption by 142 (± 34) kcal (p < 0.001) or 9.3% due to saccharide capsules. Conclusion A very low-calorie saccharide preload considerably reduces subsequent food intake leading to decreased overall calorie consumption. A saccharide preload before meals could, therefore, be a promising support for reducing caloric intake. German Clinical Trials Register DRKS00010281 (date of registration: 11.04.2016)

scholarly journals Low-dose Pramlintide Reduced Food Intake and Meal Duration in Healthy, Normal-Weight Subjects*

Obesity ◽  
2007 ◽  
Vol 15 (5) ◽  
pp. 1179-1186 ◽  
Author(s):  
Ian Chapman ◽  
Barbara Parker ◽  
Selena Doran ◽  
Christine Feinle-Bisset ◽  
Judith Wishart ◽  
...  
Keyword(s):  
Food Intake ◽  
Low Dose ◽  
Normal Weight

Serotonin type-3 receptors mediate cholecystokinin-induced satiation through gastric distension

2006 ◽  
Vol 291 (1) ◽  
pp. R115-R123 ◽  
Author(s):  
Matthew R. Hayes ◽  
Fiona M. Chory ◽  
Claire A. Gallagher ◽  
Mihai Covasa
Keyword(s):  
Food Intake ◽  
Gastric Distension ◽  
Sucrose Intake ◽  
Gastric Balloon ◽  
Sham Feeding ◽  
Balloon Distension ◽  
Type 3

We have previously shown that serotonin type-3 (5-HT3) receptors mediate cholecystokinin (CCK)-induced satiation and that this effect is dependent on postoropharyngeal feedback. However, the independent contributions of gastric and intestinal feedback in 5-HT3 receptor mediation of suppression of food intake by CCK have not been determined. Using a sham-feeding preparation combined with intraduodenal sucrose infusion, we show that blockade of 5-HT3 receptors by ondansetron (1 mg/kg ip) had no effect on suppression of sham feeding by intraduodenal 15% sucrose infusion (4 ml/10 min), CCK (2 μg/kg ip) administration, or the combination of the two treatments. In separate experiments consisting of either sham-feeding rats that received gastric distension with the use of a balloon or real-feeding rats whose stomachs were distended using gastric loads of saline after the occlusion of the pylorus, we tested the hypothesis that gastric feedback signals are necessary for activation of 5-HT3 receptors. Ondansetron significantly attenuated suppression of sham sucrose intake after a 10-ml gastric balloon distension (30.5 ± 2.2 vs. 20.2 ± 2.2 ml, respectively) and gastric distension combined with CCK (21.9 ± 1.4 vs. 12.0 ± 1.7 ml, respectively). When intestinal feedback was eliminated in a real-feeding paradigm by closing the pylorus using a cuff preparation, ondansetron attenuated suppression of sucrose intake produced by a 10-ml saline gastric load (6.8 ± 0.7 vs. 4.2 ± 0.4 ml, respectively). Finally, when CCK (1 μg/kg) was administered in combination with a 5-ml saline gastric load in a real-feeding preparation, ondansetron significantly attenuated suppression of sucrose intake by CCK (9.0 ± 0.9 vs. 6.3 ± 0.5 ml, respectively), as well as the enhanced suppression of intake by CCK plus gastric load (6.9 ± 0.6 vs. 4.6 ± 0.5 ml, respectively). These findings demonstrate that CCK-induced activation of 5-HT3 receptors requires gastric, but not intestinal feedback.

Cholecystokinin (CCK-8) affects gastric pressure and ratings of hunger and fullness in women

1992 ◽  
Vol 263 (2) ◽  
pp. R452-R456 ◽  
Author(s):  
P. M. Melton ◽  
H. R. Kissileff ◽  
F. X. Pi-Sunyer
Keyword(s):  
Food Intake ◽  
Neural Activity ◽  
Pressure Rise ◽  
Gastric Distension ◽  
Gastric Balloon ◽  
Maximum Volume ◽  
Gastric Pressure ◽  
Gastric Contractions ◽  
Distended Stomach

Cholecystokinin (CCK) may affect food intake by augmenting neural activity from the distended stomach, thereby amplifying satiety signals. To test the hypothesis that subjects would report more fullness and less hunger with gastric distension when CCK-8 (112 ng/min) was infused than when saline was infused, a gastric balloon was inflated in the stomachs of four women. When the balloon was inflated to 500 ml, there was no difference in gastric pressure between the CCK-8 and saline conditions. Nonetheless, ratings of fullness were higher with CCK-8 administration. When the balloon was inflated to the maximum volume tolerated, the pressure rise was significantly smaller with CCK-8 infusion. In addition, fullness ratings rose and hunger ratings declined more steeply in relation to gastric pressure when CCK-8 was infused. In all conditions, gastric contractions were practically abolished with CCK-8 infusion. CCK-8 relaxed the stomach and concurrently sensitized the subjects to gastric pressure.

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