Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake

2007 ◽  
Vol 293 (4) ◽  
pp. R1490-R1494 ◽  
Author(s):  
Chun Min Lo ◽  
Dian Ming Zhang ◽  
Kevin Pearson ◽  
Liyun Ma ◽  
William Sun ◽  
...  
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Intraperitoneal Administration ◽  
Significant Inhibition ◽  
Meal Size ◽  
Saline Control ◽  
Reduce Food Intake ◽  
Satiation Effect ◽  
Threshold Levels ◽  
Cck1 Receptor

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are peptides that act both peripherally and centrally to reduce food intake by decreasing meal size. The present study examined the effects of intraperitoneally administered bolus doses of recombinant apo AIV, CCK-8, and a combination of subthreshold doses of apo AIV and CCK on 4-h food intake in rats that were fasted overnight. Apo AIV at 100 μg/kg reduced food intake significantly relative to the saline control for 1 h, as did doses of CCK-8 at or above 0.125 μg/kg. Doses of apo AIV (50 μg/kg) or CCK (0.06 μg/kg) alone had no effect on food intake. However, when these subthreshold doses of apo AIV and CCK were administered together, the combination produced a significant inhibition of food intake relative to saline controls ( P < 0.001), and the duration of the effect was longer than that caused by the administration of either apo AIV or CCK alone. The satiation effect produced by CCK-8 + apo AIV was attenuated by lorglumide, a CCK1 receptor antagonist. We conclude that, whereas the intraperitoneal administration of doses of either recombinant apo AIV or CCK at or above threshold levels reduces food intake, the coadministration of subthreshold doses of the two peptides is highly satiating and works via CCK1 receptor.

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 Hindbrain administration of NMDA receptor antagonist AP-5 increases food intake in the rat

2006 ◽  
Vol 290 (3) ◽  
pp. R642-R651 ◽  
Author(s):  
Chun-Yi Hung ◽  
M. Covasa ◽  
R. C. Ritter ◽  
G. A. Burns
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Intraperitoneal Injection ◽  
Sucrose Solution ◽  
Nmda Receptor Antagonist ◽  
Saline Control ◽  
Sucrose Intake ◽  
Mk 801

Hindbrain administration of MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) channel blocker, increases meal size, suggesting NMDA receptors in this location participate in control of food intake. However, dizocilpine (MK-801) reportedly antagonizes some non-NMDA ion channels. Therefore, to further assess hindbrain NMDA receptor participation in food intake control, we measured deprivation-induced intakes of 15% sucrose solution or rat chow after intraperitoneal injection of either saline vehicle or d(-)-2-amino-5-phosphonopentanoic acid (AP5), a competitive NMDA receptor antagonist, to the fourth ventricular, or nucleus of the solitary tract (NTS). Intraperitoneal injection of AP5 (0.05, 0.1, 1.0, 3.0, and 5.0 mg/kg) did not alter 30-min sucrose intake at any dose (10.7 ± 0.4 ml, saline control) (11.0 ± 0.8, 11.2 ± 1.0, 11.2 ± 1.0, 13.1 ± 2.2, and 11.0 ± 1.9 ml, AP5 doses, respectively). Fourth ventricular administration of both 0.2 μg (16.7 ± 0.6 ml) and 0.4 μg (14.9 ± 0.5 ml) but not 0.1 and 0.6 μg of AP5 significantly increased 60-min sucrose intake compared with saline (11.2 ± 0.4 ml). Twenty-four hour chow intake also was increased compared with saline (AP5: 31.5 ± 0.1 g vs. saline: 27.1 ± 0.6 g). Furthermore, rats did not increase intake of 0.2% saccharin after fourth ventricular AP5 administration (AP5: 9.8 ± 0.7ml, vs. saline: 10.5 ± 0.5ml). Finally, NTS AP5 (20 ng/30 nl) significantly increased 30- (AP5: 17.2 ± 0.7 ml vs. saline: 14.6 ± 1.7 ml), and 60-min (AP5: 19.4 ± 0.6 ml vs. saline: 15.5 ± 1.4 ml) sucrose intake, as well as 24-h chow intake (AP5: 31.6 ± 0.3 g vs. saline: 26.1 ± 1.2 g). These results support the hypothesis that hindbrain NMDA receptors participate in control of food intake and suggest that this participation also may contribute to control of body weight over a 24-h period.

Hypothalamic dopaminergic receptor expressions in anorexia of tumor-bearing rats

2001 ◽  
Vol 281 (6) ◽  
pp. R1907-R1916 ◽  
Author(s):  
Tomoi Sato ◽  
Michael M. Meguid ◽  
Sergueï O. Fetissov ◽  
Chung Chen ◽  
Lihua Zhang
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Meal Size ◽  
Feeding Pattern ◽  
Hypothalamic Nucleus ◽  
Receptor Subtypes ◽  
Dopaminergic Receptor ◽  
Receptor Mrna ◽  
Tumor Bearing ◽  
Free Feeding

Our past microdialysis studies in ventromedial hypothalamic nucleus (VMN) and lateral hypothalamic area (LHA) of changes in dopamine concentrations in response to changes in food intake [characterized as feeding pattern (changes in meal number and size)] in anorexia of cancer show abnormal presynaptic dopaminergic neurotransmission. To determine postsynaptic receptor status, studies were done in tumor-bearing (TB) and non-tumor-bearing (NTB) free-feeding control rats while continuously measuring their food intake via a rat eater meter. When TB rats developed anorexia, TB and control rats were killed, and postsynaptic D1- and D2-receptor mRNA expression in LHA and VMN were measured via RT-PCR. At anorexia, food intake decreased initially by a decrease in meal number, whereas a concurrent increase in meal size occurred for 24 h in an attempt to maintain food intake constant. Then meal size also decreased. At this time, D1- and D2-receptor mRNA expressions in LHA and VMN of TB vs. controls were significantly upregulated. Verification of D1- or D2-receptor changes to changes in meal number and size at anorexia was made by injection of intra-VMN or -LHA dopaminergic receptor antagonists. Intra-VMN D1-receptor antagonist (SCH-23390) in TB rats decreased food intake mainly via a decrease in meal size. Intra-VMN D2-receptor antagonist (sulpiride) in TB rats increased food intake via an increase in meal number and in NTB free-feeding rats by an increase in meal size. Intra-LHA D1-receptor antagonist in TB rats had no effect on food intake or feeding pattern. Intra-LHA D2-receptor antagonist in TB and in NTB free-feeding rats increased food intake via an increase in meal number. Our data provide evidence that postsynaptic dopaminergic receptor subtypes in the hypothalamus are involved in the regulation of meal size, meal number, and thus food intake in anorectic TB rats.

Hindbrain GRP receptor blockade antagonizes feeding suppression by peripherally administered GRP

1996 ◽  
Vol 271 (1) ◽  
pp. R180-R184 ◽  
Author(s):  
E. E. Ladenheim ◽  
J. E. Taylor ◽  
D. H. Coy ◽  
K. A. Moore ◽  
T. H. Moran
Keyword(s):  
Food Intake ◽  
Critical Role ◽  
Intraperitoneal Administration ◽  
Reduce Food Intake ◽  
Sprague Dawley ◽  
Glucose Intake ◽  
Sprague Dawley Rats ◽  
Feeding Effects ◽  
Grp Receptors ◽  
The Relationship

Bombesin (BN)-like peptides injected peripherally or centrally suppress food intake in rats. The relationship between the central and peripheral actions of BN is unknown. However, experimental evidence supports a critical role for the caudal hindbrain in mediating the feeding effects of BN. To investigate this relationship further, we examined the ability of fourth ventricular infusion of a specific gastrin-releasing peptide (GRP) antagonist, [D-F5, Phe6, D-Ala11]BN-(6-13) methyl ester (BN-ME), to block suppression of glucose intake (0.5 kcal/ml) produced by intraperitoneal administration of GRP-(18-27) in 5-h food-deprived male Sprague-Dawley rats (n = 10). We found that fourth ventricular administration of 10, 32, and 100 ng BN-ME blocked the suppression of glucose intake produced by peripherally administered 10 nmol/kg GRP-(18-27). The most effective dose of BN-ME (100 ng) blocked the ability of peripheral injection of GRP-(18-27) to inhibit glucose intake but had no effect on intake when given alone. These results demonstrate that the availability of caudal hindbrain GRP receptors is necessary for peripherally administered GRP-(18-27) to reduce food intake in rats.

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.

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.

Endogenous cholecystokinin reduces food intake and increases Fos-like immunoreactivity in the dorsal vagal complex but not in the myenteric plexus by CCK1 receptor in the adult rat

2007 ◽  
Vol 292 (3) ◽  
pp. R1071-R1080 ◽  
Author(s):  
Cherese N. Sullivan ◽  
Shannon J. Raboin ◽  
Stephen Gulley ◽  
Ntwenzi T. Sinzobahamvya ◽  
Gary M. Green ◽  
...  
Keyword(s):  
Food Intake ◽  
Vagus Nerve ◽  
Receptor Antagonist ◽  
Myenteric Plexus ◽  
Dorsal Vagal Complex ◽  
Adult Rats ◽  
Myenteric Neurons ◽  
Adult Rat ◽  
Cck1 Receptor ◽  
First Time

We hypothesized that endogenous CCK reduces food intake by activating the dorsal vagal complex (DVC) and the myenteric neurons of the gut. To test this hypothesis, adult rats were given camostat mesilate; a nonnutrient releaser of endogenous CCK, by orogastric gavage, and Fos-like immunoreactivity (Fos-LI) was quantified in the DVC and the myenteric plexus. The results for endogenous CCK were compared with those for exogenous CCK-8. Exogenous CCK-8 reduced food intake and stimulated Fos-LI in the DVC and in myenteric neurons of the duodenum and jejunum. In comparison, endogenous CCK reduced food intake and increased DVC Fos-LI but did not increase Fos-LI in the myenteric plexus. Similar to CCK-8, devazepide, a specific CCK1 receptor antagonist, and not L365,260, a specific CCK2 receptor antagonist, attenuated the reduction of food intake by camostat. In addition, Fos-LI in the DVC in response to both exogenous CCK-8 and camostat administration was significantly attenuated by vagotomy, as well as by blocking CCK1 receptors. These results demonstrate for the first time that reduction of food intake in adult rats by endogenous CCK released by a nonnutrient mechanism requires CCK1 receptors, the vagus nerve, and activation of the DVC, but not the myenteric plexus.

Cholecystokinin octapeptide decreases food intake in white-crowned sparrows

1993 ◽  
Vol 264 (5) ◽  
pp. R852-R856
Author(s):  
R. D. Richardson ◽  
T. Boswell ◽  
S. C. Weatherford ◽  
J. C. Wingfield ◽  
S. C. Woods
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Mammalian Species ◽  
Meal Size ◽  
Dark Cycle ◽  
Cholecystokinin Octapeptide ◽  
Dose Dependent Fashion ◽  
Cck Receptor Antagonist ◽  
Dose Dependent ◽  
Short Days

White-crowned sparrows maintained on short days (9:15-h light-dark cycle) were peripherally injected with 1.0, 4.0, and 16 micrograms/kg ip of cholecystokinin octapeptide (CCK-8). Meal size over the subsequent 30 min was significantly depressed in a dose-dependent fashion. Water intake was not affected. The anorexic effect caused by 4.0 micrograms/kg was attenuated by 100 micrograms/kg of the type-A CCK receptor antagonist MK-329 but not by 300 micrograms/kg of the type-B CCK receptor antagonist L 365,260, suggesting that CCK-induced suppression of food intake in this species is mediated by a CCK-A receptor. Administration of both CCK-A and CCK-B receptor antagonists alone resulted in no change in meal size. These experiments suggest that white-crowned sparrows, when weight stable, respond to CCK-8 in a manner comparable with several mammalian species.

scholarly journals Central Control of Body Weight and Appetite

2008 ◽  
Vol 93 (11_supplement_1) ◽  
pp. s37-s50 ◽  
Author(s):  
Stephen C. Woods ◽  
David A. D'Alessio
Keyword(s):  
Food Intake ◽  
Body Fat ◽  
Energy Homeostasis ◽  
Evidence Synthesis ◽  
Treatment Options ◽  
Meal Size ◽  
Reduce Food Intake ◽  
Therapeutic Goals ◽  
Therapeutic Implications ◽  
Adiposity Signals

ABSTRACT Context Energy balance is critical for survival and health, and control of food intake is an integral part of this process. This report reviews hormonal signals that influence food intake and their clinical applications. Evidence Acquisition A relatively novel insight is that satiation signals that control meal size and adiposity signals that signify the amount of body fat are distinct and interact in the hypothalamus and elsewhere to control energy homeostasis. This review focuses upon recent literature addressing the integration of satiation and adiposity signals and therapeutic implications for treatment of obesity. Evidence Synthesis During meals, signals such as cholecystokinin arise primarily from the GI tract to cause satiation and meal termination; signals secreted in proportion to body fat such as insulin and leptin interact with satiation signals and provide effective regulation by dictating meal size to amounts that are appropriate for body fatness, or stored energy. Although satiation and adiposity signals are myriad and redundant and reduce food intake, there are few known orexigenic signals; thus, initiation of meals is not subject to the degree of homeostatic regulation that cessation of eating is. There are now drugs available that act through receptors for satiation factors and which cause weight loss, demonstrating that this system is amenable to manipulation for therapeutic goals. Conclusions Although progress on effective medical therapies for obesity has been relatively slow in coming, advances in understanding the central regulation of food intake may ultimately be turned into useful treatment options.

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