scholarly journals Leptin inhibits gastric emptying in rats: role of CCK receptors and vagal afferent fibers

2007 ◽  
pp. 315-322 ◽  
Author(s):  
B Çakır ◽  
Ö Kasımay ◽  
E Devseren ◽  
BÇ Yeğen
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Receptor Blocker ◽  
Adrenergic Blockade ◽  
Phenol Red ◽  
Gastric Emptying Rate ◽  
Cck Receptors ◽  
Afferent Fibers ◽  
Cephalic Phase ◽  
Vagal Afferent

Leptin regulates energy homeostasis and body weight by balancing energy intake and expenditure. It was recently reported that leptin, released into the gut lumen during the cephalic phase of gastric secretion, is capable of initiating intestinal nutrient absorption. Vagal afferent neurons also express receptors for both CCK and leptin, which are believed to interact in controlling food intake. The present study was undertaken to investigate the central and peripheral effects of leptin on gastric emptying rate. Under anesthesia, male Sprague-Dawley rats (250-300 g) were fitted with gastric Gregory cannulas (n=12) and some had additional cerebroventricular cannulas inserted into their right lateral ventricles. Following recovery, the rate of gastric emptying of saline (300 mOsm/kg H(2)O) was determined after instillation into the gastric fistula (3 ml, 37 degrees C, containing phenol red, 60 mg/l as a non-absorbable dilution marker). Gastric emptying rate was determined from the volume and phenol red concentrations recovered after 5 min. Leptin, injected intraperitoneally (i.p.; 10, 30, 60, 100 microg/kg) or intracerebroventricularly (i.c.v.; 5, 15 microg/rat) 15 min before the emptying, delayed gastric emptying rate of saline at the dose of 30 microg/kg or 15 microg/rat (p<0.001). When CCK(1) receptor blocker L-364,718 (1 mg/kg, i.p.), CCK(2) receptor blocker L-365,260 (1 mg/kg, ip) or adrenergic ganglion blocker bretylium tosylate (15 mg/kg, i.p.) was administered 15 min before ip leptin (30 microg/kg) injections, leptin-induced delay in gastric emptying was abolished only by the CCK(1) receptor blocker (p<0.001). However, the inhibitory effect of central leptin on gastric emptying was reversed by adrenergic blockade, but not by either CCK antagonists. Our results demonstrated that leptin delays gastric emptying. The peripheral effect of leptin on gastric motility appears to be mediated by CCK(1) receptors, suggesting the release of CCK and the involvement of vagal afferent fibers. On the other hand, the central effect of leptin on gastric emptying is likely to be mediated by adrenergic neurons. These results indicate the existence of a functional interaction between leptin and CCK receptors leading to inhibition of gastric emptying and short-term suppression of food intake, providing an additional feedback control in producing satiety.

scholarly journals The common hepatic branch of the vagus is not required to mediate the glycemic and food intake suppressive effects of glucagon-like-peptide-1

2011 ◽  
Vol 301 (5) ◽  
pp. R1479-R1485 ◽  
Author(s):  
Matthew R. Hayes ◽  
Scott E. Kanoski ◽  
Bart C. De Jonghe ◽  
Theresa M. Leichner ◽  
Amber L. Alhadeff ◽  
...  
Keyword(s):  
Food Intake ◽  
Vagal Afferents ◽  
Oral Glucose ◽  
Afferent Fibers ◽  
The Common ◽  
Vagal Afferent ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
And Control ◽  
Hepatic Branch

The incretin and food intake suppressive effects of intraperitoneally administered glucagon-like peptide-1 (GLP-1) involve activation of GLP-1 receptors (GLP-1R) expressed on vagal afferent fiber terminals. Central nervous system processing of GLP-1R-driven vagal afferents results in satiation signaling and enhanced insulin secretion from pancreatic-projecting vagal efferents. As the vast majority of endogenous GLP-1 is released from intestinal l-cells following ingestion, it stands to reason that paracrine GLP-1 signaling, activating adjacent GLP-1R expressed on vagal afferent fibers of gastrointestinal origin, contributes to glycemic and food intake control. However, systemic GLP-1R-mediated control of glycemia is currently attributed to endocrine action involving GLP-1R expressed in the hepatoportal bed on terminals of the common hepatic branch of the vagus (CHB). Here, we examine the hypothesis that activation of GLP-1R expressed on the CHB is not required for GLP-1's glycemic and intake suppressive effects, but rather paracrine signaling on non-CHB vagal afferents is required to mediate GLP-1's effects. Selective CHB ablation (CHBX), complete subdiaphragmatic vagal deafferentation (SDA), and surgical control rats received an oral glucose tolerance test (2.0 g glucose/kg) 10 min after an intraperitoneal injection of the GLP-1R antagonist, exendin-(9–39) (Ex-9; 0.5 mg/kg) or vehicle. CHBX and control rats showed comparable increases in blood glucose following blockade of GLP-1R by Ex-9, whereas SDA rats failed to show a GLP-1R-mediated incretin response. Furthermore, GLP-1(7–36) (0.5 mg/kg ip) produced a comparable suppression of 1-h 25% glucose intake in both CHBX and control rats, whereas intake suppression in SDA rats was blunted. These findings support the hypothesis that systemic GLP-1R mediation of glycemic control and food intake suppression involves paracrine-like signaling on GLP-1R expressed on vagal afferent fibers of gastrointestinal origin but does not require the CHB.

Gastric loads potentiate inhibition of food intake produced by a cholecystokinin analogue

1991 ◽  
Vol 261 (5) ◽  
pp. R1141-R1146 ◽  
Author(s):  
G. J. Schwartz ◽  
L. A. Netterville ◽  
P. R. McHugh ◽  
T. H. Moran
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Threshold Dose ◽  
Gastric Distension ◽  
Cck Receptors ◽  
Load Combination ◽  
Glucose Intake ◽  
Dose Dependent Fashion ◽  
Inhibit Food Intake ◽  
Long Acting

We have proposed that cholecystokinin's (CCK) inhibition of gastric emptying contributes to its ability to inhibit food intake. To directly test this hypothesis in rats, the effect of the presence of a 5-ml gastric saline load on the ability of a long-acting cholecystokinin analogue U-67827E (0.1-10.0 nmol/kg) to inhibit intake of a 0.5 kcal/ml glucose solution was measured. The CCK analogue alone inhibited intake at a threshold dose of 2.5 nmol/kg. Although lower doses of the CCK analogue alone had no effect on subsequent glucose intake, when combined with the gastric load such doses did significantly inhibit intake. Thus the presence of a gastric load reduced the threshold dose of the CCK analogue required to inhibit intake. Furthermore, at suprathreshold doses, the peptide-load combination suppressed intake more than the peptide alone. In addition, administration of 0.5 and 5.0 nmol/kg doses of the CCK analogue inhibited gastric emptying at 10, 20, and 30 min in a dose-dependent fashion. The CCK analogue's inhibition of food intake and gastric emptying were reversed by pretreatment with 100 micrograms/kg L364,718, indicating that the analogue was having its effects by interacting with specific type A CCK receptors. Together these data support the notion that CCK satiety derives from an integration of the visceral afferent signals generated by CCK's promotion of gastric distension and those produced directly by CCK.

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.

Pancreatic secretion stimulated by CCK is not mediated by capsaicin-sensitive vagal afferent pathway in awake rats

1996 ◽  
Vol 270 (5) ◽  
pp. G881-G886 ◽  
Author(s):  
D. Guan ◽  
W. T. Phillips ◽  
G. M. Green
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Pancreatic Secretion ◽  
Fluid Secretion ◽  
Afferent Pathway ◽  
Afferent Pathways ◽  
Intraduodenal Infusion ◽  
Anesthetized Rats ◽  
Vagal Afferent ◽  
Awake Rats

A capsaicin-sensitive vagal afferent pathway was reported to mediate the effect of endogenous cholecystokinin (CCK) on pancreatic secretion in anesthetized rats. Because neural blockade affects pancreatic secretion much less in awake than in anesthetized rats, the effect of capsaicin ablation of vagal afferent pathways on pancreatic secretion stimulated by endogenous CCK was examined in awake rats. During surgery, abdominal vagal trunks were exposed, and 0.1 ml of capsaicin (10 mg/ml) was applied to the vagal trunks. Ablation of the vagal afferent pathway was assessed by the ability of intraperitoneal cholecystokinin octapeptide (CCK-8) to suppress food intake and inhibit gastric emptying. Endogenous CCK release was stimulated by diversion of bile pancreatic juice from the intestine and by intraduodenal infusion of casein. Pancreatic protein and fluid secretion were significantly increased by both treatments, and the responses were unaffected by capsaicin. Intraperitoneal CCK-8 markedly inhibited food intake and gastric emptying, and both effects were significantly attenuated in capsaicin-treated rats, indicating that capsaicin treatment successfully ablated vagal afferent fibers. It is concluded that CCK-stimulated pancreatic secretion in rats is not mediated by a vagal afferent pathway.

Gastric loads and cholecystokinin synergistically stimulate rat gastric vagal afferents

1993 ◽  
Vol 265 (4) ◽  
pp. R872-R876 ◽  
Author(s):  
G. J. Schwartz ◽  
P. R. McHugh ◽  
T. H. Moran
Keyword(s):  
Food Intake ◽  
Vagal Afferents ◽  
Sufficient Information ◽  
Afferent Activity ◽  
Combined Load ◽  
Synergistic Inhibition ◽  
Afferent Fibers ◽  
Inhibit Food Intake ◽  
Vagal Afferent ◽  
Afferent Response

Both gastric preloads and exogenous cholecystokinin (CCK) administration inhibit food intake, and combinations of preloads and CCK suppress feeding to a greater degree than either stimulus delivered alone. A role for the vagus nerve in mediating CCK's inhibition of food intake has been proposed, and gastric vagal afferent fibers respond to both gastric loads and local CCK infusions. To examine whether combined load and CCK stimuli may synergistically augment gastric neural afferent activity at the level of the peripheral vagus, we have examined the gastric vagal afferent responses (n = 8) to a range of gastric saline loads (1, 2, and 3 ml) and exogenous close celiac arterial CCK (10 and 100 pmol) when administered alone or in combination. Gastric loads ineffective in eliciting a significant increase in vagal afferent activity when administered alone became effective when combined with doses of CCK that were subthreshold for the production of a vagal afferent response. Gastric loads that alone were effective in producing a significant vagal afferent response yielded an even greater response when administered in combination with both subthreshold and suprathreshold doses of CCK. These data demonstrate that, in rats, signals produced by combined gastric load and exogenous CCK administration are integrated peripherally and interact synergistically. These results suggest that signals arising from the vagus may provide sufficient information for the synergistic inhibition of food intake produced by combinations of gastric loads and exogenous CCK.

scholarly journals Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms

1997 ◽  
Vol 273 (4) ◽  
pp. G920-G927 ◽  
Author(s):  
Neşe I˙meryüz ◽  
Berrak Ç. Yeğen ◽  
Ayhan Bozkurt ◽  
Tamer Coşkun ◽  
Maria L. Villanueva-Peñacarrillo ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Acid Secretion ◽  
Methyl Cellulose ◽  
Gastric Fistula ◽  
Adrenergic Blockade ◽  
Central Administration ◽  
Gastric Function ◽  
Vagal Afferent ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Exogenous administration of glucagon-like peptide-1-(7—36) amide (GLP-1), an insulinotropic hormone, inhibits gastric emptying and acid secretion in humans. The role of GLP-1 as a regulator of gastric function is elusive. In gastric fistula rats, vagal afferent denervation and peripheral administration of the GLP-1 receptor antagonist exendin(9—39) amide enhanced emptying of a glucose meal, whereas intracerebroventricular exendin was ineffective. The rate of saline emptying was attenuated by peripheral as well as by central administration of GLP-1, and pretreatment with exendin by the respective routes reversed the inhibition by GLP-1. Vagal afferent denervation abolished the central and peripheral action of GLP-1 on gastric emptying. Neither peripheral cholinergic nor adrenergic blockade altered the delay of methyl cellulose meal emptying by intracisternal GLP-1 injection. Acid secretion in conscious pylorus-ligated rats was inhibited by intracisternal GLP-1 administration, whereas systemic GLP-1 was ineffective. These results support the notion that GLP-1 receptors participate in the central and peripheral regulation of gastric function. Furthermore, vagal afferent nerves mediate the inhibitory action of GLP-1 on gastric motor function. GLP-1 may be a candidate brain-gut peptide that acts as a physiological modulator of gastric function.

Effect of a cholecystokinin-A receptor blocker on protein-induced food intake suppression in rats

1997 ◽  
Vol 272 (6) ◽  
pp. R1826-R1833 ◽  
Author(s):  
L. Trigazis ◽  
A. Orttmann ◽  
G. H. Anderson
Keyword(s):  
Amino Acids ◽  
Food Intake ◽  
Dietary Protein ◽  
Corn Starch ◽  
Corn Oil ◽  
Receptor Blocker ◽  
Egg Albumin ◽  
Cck Receptors ◽  
Chicken Egg

To test the hypothesis that only dietary protein (Pro; chicken egg albumin) and not amino acids (AA), carbohydrates (CHO; cornstarch), or fats (Fat; corn oil) produces a satiating effect via cholecystokinin (CCK) receptors, devazepide was coadministered with each macronutrient. Given alone (in 4 ml ig), Pro (0.75, 1.0, and 1.5 g), AA (1.0 g), CHO (1.4 g), and Fat (2.4 g) suppressed (P < 0.05) food intake in the first hour by 0.5, 0.8, and 1.1 g; 1.9 g; and 1.0 g, respectively, and in the first 2 h of feeding by 0.8, 1.2, and 1.3 g; 1.7 g; 0.7 g; and 1.5 g, respectively. When coadministered with devazepide (0.5 mg/kg body wt ig), the suppression of food intake caused by Pro, AA, CHO, and Fat treatments was modulated in the first hour by 60, 50, and 55%; 16%, 11%; and 10%, respectively, and during 0-2 h by 63, 92, and 54%; 29%; 0%; and -20%, respectively. Devazepide (0.5 mg/kg) given intraperitoneally also modulated Pro intake suppression during the first hour by 33% and during 0-2 h by 79%. Devazepide appears to interact with mechanisms of Pro-induced food intake suppression, but not AA-, Fat-, or CHO-induced food intake suppression. These studies provide evidence that CCK receptors play a role in Pro (albumin)- but not AA-, CHO (corn starch)-, or Fat (corn oil)-induced food intake suppression in rats.

CCK-8 decreases food intake and gastric emptying after pylorectomy or pyloroplasty

1988 ◽  
Vol 255 (1) ◽  
pp. R113-R116
Author(s):  
G. P. Smith ◽  
J. Falasco ◽  
T. H. Moran ◽  
K. M. Joyner ◽  
J. Gibbs
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Binding Sites ◽  
Specific Binding ◽  
Circular Muscle ◽  
Pyloric Sphincter ◽  
Inhibitory Effects ◽  
Cck Receptors ◽  
Adult Rat ◽  
Pyloric Muscle

Specific binding sites for cholecystokinin (CCK) in the gastrointestinal tract of the adult rat are limited to the gastroduodenal region and are concentrated in the circular muscle of the pyloric sphincter. To determine the relationship of these pyloric muscle binding sites to the inhibition by CCK of food intake and of gastric emptying, these inhibitory effects of CCK were investigated in rats that had the pyloric sphincter surgically removed or that had the pyloric sphincter contractile mechanism damaged by a pyloroplasty procedure. CCK-8 decreased food intake and gastric emptying significantly in rats after pylorectomy or pyloroplasty. This demonstrates that an intact pyloric sphincter is not necessary for these inhibitory effects in rats. Because we found autoradiographic evidence for CCK receptors near the gastroduodenal anastomosis, however, the results suggest either that these receptors mediated the inhibition of food intake and emptying by CCK-8 or that these effects depend on CCK receptors in other locations.

scholarly journals Effect of an abrupt switch from a milk-based to a fibre-based diet on gastric emptying rates in pigs: difference between origins of fibre

2004 ◽  
Vol 92 (6) ◽  
pp. 913-920 ◽  
Author(s):  
Gaëlle Boudry ◽  
Sylvie Guérin ◽  
Charles Henri Malbert
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
High Frequency ◽  
Gastric Emptying Rate ◽  
Daily Food Intake ◽  
Daily Food ◽  
Before And After ◽  
Milk Substitute ◽  
Dietary Switch ◽  
Fibrous Diet

A characteristic dietary feature at weaning is a switch from a milk-based to plant-based diet, i.e. from a non-fibrous to a fibrous diet. The present study aimed to evaluate the effects of such an abrupt dietary switch on gastric emptying rate in pigs maintained on a milk substitute after weaning. Eighteen piglets were kept on a milk substitute for 5 weeks after weaning and were then switched to wheat-based or barley-based diets or kept on the milk substitute (six piglets per group). All piglets were fasted for 1d before the switch and daily food intake was then increased linearly to reach initial values within 3d. The gastric emptying rate was measured by γ-scintigraphy before and after the switch. Corpo-antral peristalsis was also evaluated by the use of high-frequency scintigraphic frames. The gastric emptying rate of the wheat-based diet was accelerated on days 1 to 3 after the switch, but was similar to that in the milk-substitute group thereafter. This acceleration was concomitant with an enhanced frequency of corpo-antral waves on days 2 and 3. Conversely, the gastric emptying rate of the barley-based diet tended to be enhanced on day 2, but was delayed on days 4 and 5, without any change in frequency of corpo-antral waves. We conclude that a switch from a non-fibrous to a fibrous diet alters the gastric emptying rate differently depending on the type of dietary fibre.

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