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.

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.

scholarly journals Circulating GLP-1 and CCK-8 reduce food intake by capsaicin-insensitive, nonvagal mechanisms

2012 ◽  
Vol 302 (2) ◽  
pp. R264-R273 ◽  
Author(s):  
Jingchuan Zhang ◽  
Robert C. Ritter
Keyword(s):  
Food Intake ◽  
Plasma Concentrations ◽  
Vagal Afferents ◽  
Reduce Food Intake ◽  
Sucrose Intake ◽  
Paracrine Effects ◽  
Distal Small Intestine ◽  
Nodose Ganglia ◽  
Glucagon Like Peptide ◽  
The Brain

Previous reports suggest that glucagon-like peptide (GLP-1), a peptide secreted from the distal small intestine, is an endocrine satiation signal. Nevertheless, there are conflicting reports regarding the site where circulating GLP-1 acts to reduce food intake. To test the hypothesis that vagal afferents are necessary for reduction of food intake by circulating GLP-1, we measured intake of 15% sucrose during intravenous GLP-1 infusion in intact, vagotomized, and capsaicin-treated rats. We also measured sucrose intake during intravenous infusion of cholecystokinin, a peptide known to reduce food intake via abdominal vagal afferents. We found that reduction of intake by GLP-1 was not diminished by capsaicin treatment or vagotomy. In fact, reduction of sucrose intake by our highest GLP-1 dose was enhanced in vagotomized and capsaicin-treated rats. Intravenous GLP-1 induced comparable increases of hindbrain c-Fos immunoreactivity in intact, capsaicin-treated, and vagotomized rats. Plasma concentrations of active GLP-1 in capsaicin-treated rats did not differ from those of controls during the intravenous infusions. Finally, capsaicin treatment was not associated with altered GLP-1R mRNA in the brain, but nodose ganglia GLP-1R mRNA was significantly reduced in capsaicin-treated rats. Although reduction of food intake by intraperitoneal cholecystokinin was abolished in vagotomized and capsaicin-treated rats, reduction of intake by intravenous cholecystokinin was only partially attenuated. These results indicate that vagal or capsaicin-sensitive neurons are not necessary for reduction of food intake by circulating (endocrine) GLP-1, or cholecystokinin. Vagal participation in satiation by these peptides may be limited to paracrine effects exerted near the sites of their secretion.

Anorexia and fat aversion induced by vertical sleeve gastrectomy is attenuated in neurotensin receptor 1 deficient mice

Endocrinology ◽  
2021 ◽  
Author(s):  
Cecilia Ratner ◽  
Jae-Hoon Shin ◽  
Chinmay Dwibedi ◽  
Valentina Tremaroli ◽  
Anette Bjerregaard ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
Food Intake ◽  
Reduce Food Intake ◽  
Vertical Sleeve Gastrectomy ◽  
Potent Effect ◽  
Neurotensin Receptor ◽  
Macronutrient Selection ◽  
Gut Hormone ◽  
Neurotensin Receptor 1 ◽  
Fat Preference

Abstract Neurotensin (NT) is an anorexic gut hormone and neuropeptide that increases in circulation following bariatric surgery in humans and rodents. We sought to determine the contribution of NT to the metabolic efficacy of vertical sleeve gastrectomy (VSG). To explore a potential mechanistic role of NT in VSG, we performed sham or VSG surgeries in diet-induced obese neurotensin receptor 1 (NTSR1) wildtype (wt) and knockout (ko) mice and compared their weight and fat mass loss, glucose tolerance, food intake, and food preference after surgery. NTSR1 ko mice had reduced initial anorexia and body fat loss. Additionally, NTSR1 ko mice had an attenuated reduction in fat preference following VSG. Results from this study suggest that NTSR1 signaling contributes to the potent effect of VSG to initially reduce food intake following VSG surgeries and potentially also on the effects on macronutrient selection induced by VSG. However, maintenance of long-term weight loss after VSG requires signals in addition to NT.

scholarly journals Polydextrose results in a dose-dependent reduction in ad libitum energy intake at a subsequent test meal

2013 ◽  
Vol 110 (5) ◽  
pp. 934-942 ◽  
Author(s):  
Nerys M. Astbury ◽  
Moira A. Taylor ◽  
Ian A. Macdonald
Keyword(s):  
Energy Intake ◽  
Test Meal ◽  
Optimal Dose ◽  
Reduce Food Intake ◽  
Dependent Manner ◽  
Food Diary ◽  
Subsequent Test ◽  
Ad Libitum ◽  
Dose Dependent ◽  
Analogue Scales

Previous studies have reported that polydextrose can reduce food intake; however, the optimal dose required to achieve this effect is currently unknown. The present study investigated the effects of consuming a range of doses of polydextrose on appetite and energy intake (EI) using a randomised within-subject, cross-over design. For this purpose, twenty-one participants (n 12 men, n 9 women) consumed an 837 kJ liquid preload containing 0 g (control), 6·3, 12·5 or 25 g polydextrose. Subjective appetite ratings were collected using visual analogue scales and an ad libitum test meal was served 90 min later. Participants recorded EI for the remainder of the day in a food diary. Test meal EI following the control preload (5756 (sem 423) kJ) was significantly higher than following the 6·3 g (5048 (sem 384) kJ), 12·5 g (4722 (sem 384) kJ) and 25 g (4362 (sem 316) kJ) preloads (P< 0·05), and EI following the 6·3 g preload was significantly higher than following the 25 g preload (P< 0·01). There were no differences in self-reported EI during the remainder of the day between the preloads containing the varying doses of polydextrose. Total EI (breakfast+preload+ad libitum test meal+remainder of the day) was significantly higher when the control preload was consumed (12 051 (sem 805) kJ) compared with either the 12·5 g (10 854 (sem 589) kJ) or 25 g (10 658 (sem 506) kJ) preload (P< 0·05). These differences in EI were not accompanied by corresponding differences in subjective appetite ratings. In summary, polydextrose effectively reduces subsequent EI in a dose-dependent manner.

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.

Intracerebroventricular Leptin Administration Reduces Food Intake in Pregnant and Lactating Mice1

2002 ◽  
Vol 227 (8) ◽  
pp. 616-619 ◽  
Author(s):  
Anahita M. Mistry ◽  
Dale R. Romsos
Keyword(s):  
Food Intake ◽  
Binding Proteins ◽  
Plasma Concentrations ◽  
High Plasma ◽  
Reduce Food Intake ◽  
Elevated Plasma ◽  
Female Mice ◽  
Pregnancy And Lactation ◽  
Pregnant Mice ◽  
Plasma Leptin

Leptin acts within the hypothalamus to diminish food intake. During pregnancy and lactation, both circulating leptin concentrations and food intake are elevated, suggesting an ineffectiveness of leptin to reduce food intake in these mice. Thus, this study tested the ability of intracerebroventricular (ICV) leptin administration to alter food intake during pregnancy and lactation. Mice during the first, second, and third trimesters of pregnancy, lactating mice on postpartum Day 7, and age-matched female mice were used. Plasma leptin concentrations averaged 2.9 ± 0.3 ng/ml in control mice, increased steadily as pregnancy progressed (3.4 ± 0.7, 29.8 ± 4.5, and 40.5 ± 0.7 ng/ml during the first, second, and third trimesters, respectively), and remained elevated on Day 7 postpartum (26.4 ± 7.8 ng/ml). Mice were food deprived for 4 h, injected ICV with vehicle or leptin (1 μg), and food intake was subsequently measured hourly for 3 hr, and after 24 hr. Vehicle-treated pregnant mice consumed marginally more food than cycling control mice, whereas nursing dams ate two to three times as much food as controls. As expected, ICV leptin administration reduced 24-hr food intake of control mice by 2 g, or ~50%. ICV-administered leptin was as effective in reducing food Intake of pregnant and lactating mice as observed in control mice. Thus, the elevated circulating leptin concentrations observed in pregnant and nursing mice did not alter the ability of ICV-administered leptin to diminish food intake. High plasma concentrations of leptin-binding proteins observed during pregnancy, and probably during lactation, may limit the amount of endogenous leptin reaching the hypothalamus, and may consequently enable increases in food intake concomitant with elevated plasma leptin during these nutritionally demanding periods.

scholarly journals Hyperosmolar Duodenal Saline Infusion Lowers Circulating Ghrelin and Stimulates Intestinal Hormone Release in Young Men

2018 ◽  
Vol 103 (12) ◽  
pp. 4409-4418 ◽  
Author(s):  
Simon Veedfald ◽  
Tongzhi Wu ◽  
Michelle Bound ◽  
Jacqueline Grivell ◽  
Bolette Hartmann ◽  
...  
Keyword(s):  
Peptide Yy ◽  
Venous Blood ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
Young Men ◽  
Saline Infusion ◽  
Intraduodenal Infusion ◽  
Gut Hormone ◽  
Double Blinded ◽  
Ghrelin Secretion

AbstractContextThe mechanisms regulating the postprandial suppression of ghrelin secretion remain unclear, but recent observations in rats indicate that an increase in duodenal osmolarity is associated with a reduction in ghrelin levels. Several hormones have been implicated in the regulation of ghrelin.ObjectiveWe hypothesized that intraduodenal infusion of a hyperosmolar solution would lower plasma ghrelin concentrations.Design, Setting, Participants, and InterventionsEighteen healthy young men were studied after an overnight fast on two occasions in a randomized double-blinded fashion. A nasoduodenal catheter was positioned and isoosmolar (300 mOsm/L) or hyperosmolar (1500 mOsm/L) saline was infused intraduodenally (4 mL/min, t = 0 to 45 minutes). Venous blood was sampled at t = −45, −30, −15, 0, 15, 30, 45, 60, 75, 90, 120, and 180 minutes.Main Outcome MeasuresPlasma concentrations of ghrelin, glucagonlike peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), glucagon, pancreatic polypeptide (PP), neurotensin (NT), peptide YY (PYY), motilin, and glucose.ResultsGhrelin concentrations were suppressed with hyperosmolar when compared with isoosmolar saline, and remained lower until t = 180 minutes. CCK, NT, GLP-1, PYY, and glucagon all increased during hyperosmolar, but not isoosmolar, saline infusion (P &lt; 0.01 for all), whereas GIP, PP, and motilin levels were not affected by either infusion.ConclusionsPlasma ghrelin concentrations are lowered, whereas CCK, GLP-1, PYY, NT, and glucagon concentrations are augmented, by hyperosmolar duodenal content in healthy individuals. These observations have implications for the evaluation of studies comparing the effects of different types and loads of nutrients and chemicals on gut hormone secretion.

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.

Low-dose pancreatic polypeptide inhibits food intake in man

2007 ◽  
Vol 97 (3) ◽  
pp. 426-429 ◽  
Author(s):  
David R. Jesudason ◽  
Mariana P. Monteiro ◽  
Barbara M. C. McGowan ◽  
Nicola M. Neary ◽  
Adrian J. Park ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Intake ◽  
Pancreatic Polypeptide ◽  
Plasma Levels ◽  
Human Study ◽  
Visual Analogue Score ◽  
Treated Group ◽  
Reduce Food Intake ◽  
Pancreatic Tumours ◽  
Gut Hormone

Pancreatic polypeptide (PP) is a gut hormone released from the pancreas in response to food ingestion and remains elevated for up to 6 h postprandially. Plasma levels are elevated in patients with pancreatic tumours. An intravenous infusion of PP has been reported to reduce food intake in man, suggesting that PP is a satiety hormone. We investigated whether a lower infusion rate of PP would induce significant alterations in energy intake. The study was randomised and double-blinded. Fourteen lean fasted volunteers (five men and nine women) received 90 min infusions of PP (5 pmol/kg per min) and saline on two separate days. The dose chosen was half that used in a previous human study which reported a decrease in appetite but at supra-physiological levels of PP. One hour after the end of the infusion, a buffet lunch was served and energy intake measured. PP infusion was associated with a significant 11 % reduction in energy intake compared with saline (2440 (se 200) v. 2730 (se 180) kJ; P < 0·05). Preprandial hunger as assessed by a visual analogue score was decreased in the PP-treated group compared to saline. These effects were achieved with plasma levels of PP within the pathophysiological range of pancreatic tumours.

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.

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