Role In Satiety Research Articles

Role of satiation in the functional response of a piscivore, largemouth bass (Micropterus salmoides)

We evaluated whether satiation regulates the predation rates of a piscivore, largemouth bass (Micropterus salmoides), in natural settings. A functional response model indicated that predation rates can be reduced by satiation when mean prey density is high or when prey encounters are highly patchy. We then used bioenergetics modeling to estimate the predation rates of individual bass in four lakes during a 16-year period and used stomach content mass in diet samples to evaluate the variability in daily predation rates. Predation rates, expressed as the proportion (p) of the maximum daily consumption rate, were low (mode = 0.3, mean = 0.4). Stomach fullness (s), expressed as the proportion of the stomach fullness associated with the maximum sustainable consumption rate, was highly variable, and 13% of all bass diets had s > 1, indicating that bass could opportunistically forage at rates exceeding their maximum sustainable rate. The low predation rates and the ability to consume prey at rates exceeding the maximum sustainable rate make it unlikely that satiation was an important constraint on bass predation rates. Thus, satiation effects widely represented in modeling studies may be a rare component in piscivore-prey interactions, while prey behavior may be a more important component governing predation rates.

Role of satiation in the functional response of a piscivore, largemouth bass (<i>Micropterus salmoides</i>)

Role of satiation in the functional response of a piscivore, largemouth bass (<i>Micropterus salmoides</i>)

Compensatory hyperphagia after fasting tracks recovery of liver energy status

Studies using metabolic inhibitors suggest that a reduction in hepatic ATP generates a stimulus that triggers feeding behavior. To investigate the relationship between changes in liver ATP and food intake under physiological conditions, we assessed changes in feeding behavior and liver adenine nucleotides during refeeding after 24 h of food deprivation. Deprived rats consumed 14 g of food in the first 3 h of refeeding; the rate of consumption declined markedly thereafter for the next 9 h, but remained higher than that seen in nonfasted rats. Fasting produced substantial reductions in ATP, ATP/ADP, and phosphorylation potential relative to fed levels. Refeeding restored liver ATP by 6 h, whereas ATP/ADP and phosphorylation potential did not fully recover until 12 h of refeeding. Restricting food intake during refeeding limited recovery of liver energy status. These results show that liver energy production recovers slowly during refeeding with a time course that parallels the compensatory change in eating behavior. These findings raise the possibility that changes in hepatic energy status play a role in satiation as well as in hunger.

Gastroduodenal motility

Several major themes emerged over the past year in the area of gastroduodenal motility. Mostly, these themes represented extensions of research areas discussed in prior reviews in this series rather than the emergence of completely new concepts. Thus, for example, considerable emphasis has again been placed on regional gastric motor function in dyspepsia and on the role of fundic relaxation and accommodation, in particular. Not surprisingly, basic physiologic research has also shown a keen interest in the regulation of fundic relaxation. One new and exciting development is the recognition of the stomach's role in satiety. The spectrum of gastric motor dysfunction in diabetes mellitus continues to be explored, and the important role of hyperglycemia in regulating gastric function has been further emphasized. More data have been provided on noninvasive alternatives to gastric motor function testing, and several studies have looked at factors that may influence variability in these various tests. There have been few innovations over the past year in the therapeutic arena; rather, the indications and limitations of current therapies have been further developed.

Satiation, capacity, and within-session responding.

Responding may change substantially over the course of a session (McSweeney, Hinson, & Cannon, 1996). The role of satiation in this effect was investigated in three experiments. Experiment 1 showed that the capacity of pigeons to consume milo over a 1-hr period was relatively stable across three different methods of measurement. In Experiment 2, pigeons were divided into two groups that differed in their capacity based on one of those measures. Key pecking was then reinforced under a variable-interval 30-s schedule with hopper durations of 2 or 5 s. According to the satiation hypothesis, subjects with small capacities should satiate faster and therefore show greater decreases in food-reinforced responding than would subjects with larger capacities. The results confirmed this prediction and showed that the magnitudes of within-session decreases were better predicted by the amount an animal consumed relative to its capacity than by absolute amount alone. In Experiment 3, each pigeon was prefed 0, 5, 15, or 25 g of milo prior to each session. Consistent with the satiation hypothesis, increases in prefeeding produced lower overall response rates in the smaller capacity subjects than in the larger capacity subjects at each level of prefeeding. These experiments demonstrate the importance of a new variable in the control of behavior, and provide a recommended technique for its measurement.

Influence of the non-competitive NMDA receptor antagonist MK-801 on 2-deoxy- d-glucose-induced hyperphagia in rats

The effects of the glutamate N-methyl- d-aspartate (NMDA) receptor antagonist (5 R,10 S)-(+)-5-methyl-10,11-dihydro-5 H-dibenzo[ a, d]cyclo-hepten-5,10-imine (MK-801) on 2-deoxy- d-glucose-induced hyperphagia were investigated in rats. MK-801 significantly increased 2-deoxy- d-glucose-elicited eating. The facilitating effects of MK-801 on 2-deoxy- d-glucose-elicited feeding were not affected by coadministration of a nitric oxide (NO) precursor, l-arginine. Because NO synthase inhibitors inhibit 2-deoxy- d-glucose-induced hyperphagia and activation of the NMDA receptor leads to NO formation, our results suggest that blockade of the NMDA receptor increases 2-deoxy- d-glucose-induced hyperphagia, which is unrelated to inhibition of NO, and that NMDA receptors may play a role in satiety.

Lean (Fa/Fa) but not obese (fa/fa) Zucker rats release cholecystokinin at PVN after a gavaged meal.

Neuropeptides play an important role in the integration of dietary signals. Cholecystokinin (CCK) has been implicated in regulating ingestive behavior, particularly satiety. The primary objective of this study was to examine whether the hyperphagia characteristic of obese (fa/fa) rats involves impaired neural CCK secretion. Dynamic release of CCK at the hypothalamic paraventricular nucleus (PVN) of age-matched lean (Fa/Fa) and obese Zucker rats was determined using push-pull perfusion. The gavage of a 10.3-kcal (6 ml) liquid diet during lights off was followed by increased CCK release in lean rats (from 13.6 +/- 1.1 to 22.1 +/- 1.4 fmol in the 1st postprandial period and 18.4 +/- 2.5 fmol in the 2nd postprandial period). An identical meal load resulted in no postprandial increase in CCK release in obese rats, despite the fact that high-K+ artificial cerebrospinal fluid evoked CCK outflow in all animals. Intubation of 6 ml of nonnutritive 1% carboxymethylcellulose had no effect. These results are consistent with the suggestion that hypothalamic CCK plays a physiological role in satiety, and they demonstrate that obese Zucker rats have blunted hypothalamic CCK release in response to dietary cues.

Serotonergic control of the organization of feeding and satiety

Studies in which serotonergic drugs were administered either systemically or directly into central sites have implicated 5-HT in the inhibitory control of feeding in mammals. In animal models and in humans, 5-HT agonists such as fenfluramine, fluoxetine and sertraline reduced the rate of eating and the size of meals in a manner suggesting that increasing serotonergic neurotransmission specifically enhanced satiation. In rodents, directly acting agonists at 5-HT 1 B , 5-HT 2 C or 5-HT 2 A receptors decreased food intake but by different behavioral mechanisms. Stimulation of the 1B and 2C subtypes may probe physiological roles in feeding and satiety. The former receptors may be involved primarily in regulating meal size and the latter more in controlling eating rate. Activation of both may be required for complete expression of behavioral satiety. By contrast, stimulating 2A sites may simply disrupt the continuity of feeding. Drugs that stimulate 5-HT 1 A autoreceptors increase food intake, presumably by acutely reducing the firing of serotonergic neurons in the brain. The hypothalamic paraventricular nucleus (PVN) has been proposed as an important terminal field in the forebrain that is involved in 5-HT's satiety role although recent studies implicate extra-PVN regions in this function. Peripherally administered 5-HT also decreases food intake in rats in a behaviorally specific manner. Studies with antagonists and with structural analogs of 5-HT revealed that 5-HT's peripheral satiety action involves 5-HT 1-like and 5-HT 2-like mechanisms. Thus, within and outside the brain, multiple pharmacological and behavioral mechanisms contribute to serotonergic functions in ingestion. The rich body of data from preclinical investigation in animals provides the foundation for therapeutic development in humans.

Feeding-related immunoreactive insulin changes in the PVN-VMH revealed by microdialysis

The presence of insulin in the brain and its anorectic effect when centrally infused are well-established today. The question of physiological and dynamic changes in brain insulin in relation to meals is still unanswered and addressed here. Immunoreactive insulin (IRI) was measured using a sensitized RIA in 30-min microdialysates from VMH and PVN nuclei during and after a scheduled meal in male Wistar rats. We indeed observed elevations in hypothalamic IRI during the first 30 min of 1-h meals with a progressive return towards premeal levels in spite of a robust satiety. When the rats were accustomed to the scheduled meals, an anticipatory rise in IRI was found in the hypothalamus, but not in the plasma, during the 30 min preceding the due time of the meal whether the meal was presented or not. This anticipatory rise was proportional to the number of repeated scheduled meals. These results first suggest that hypothalamic IRI changes reflect in some instances those in the plasma although there are exceptions that cannot be accounted for by a simple plasma-brain tissue delivery. Besides, hypothalamic IRI can hardly be proposed as a satiety signal. The present data suggest a role in satiation rather than in satiety or, perhaps, in the inhibition of the behavioral response of feeding that can include the anticipatory rise.

CNS injection of CCK in rats: effects on real and sham feeding and gastric emptying

Cholecystokinin (CCK) released from the intestine during feeding may have a physiological role in satiety. There is also evidence that activation of central CCK-containing pathways is involved in the control of feeding behavior. This study was carried out to determine whether CCK-8 administered into the lateral cerebral ventricles (lv) of rats suppresses both sham feeding (SF) and real feeding (RF). Rats with lv guides and gastric cannulas ate a liquid diet with cannulas open (SF) or closed (RF) after lv (0, 0.05, 0.5 micrograms) or intraperitoneal (ip) (0, 4 micrograms/kg) injection of CCK-8. Both RF and SF were significantly decreased by ip CCK-8. RF was also decreased in a dose-related manner after lv CCK-8, but SF was not affected by lv CCK-8. Decreased feeding after ip CCK-8 may be due in part to its suppression of gastric emptying rate (GER). To determine whether central nervous system (CNS) CCK might also be involved in the control of gastric function, GER was measured after lv (0, 0.05, 0.5 micrograms) or ip (0, 4 micrograms/kg) injection of CCK-8. GER was significantly decreased after ip CCK-8, but lv CCK-8 had no effect on GER. Although both CNS and peripheral CCK peptide systems may be involved in satiety, CNS CCK appears to depend on concurrent peripheral nutrient-related stimuli in eliciting satiety.

The role of a modulatory neuron in feeding and satiation in Aplysia: effects of lesioning of the serotonergic metacerebral cells

Food-induced arousal in Aplysia is characterized by a progressive increase in the speed and strength of biting responses elicited by a seaweed stimulus. Data from semi-intact and dissected preparations suggest that the identified, serotonergic, metacerebral cells (MCCs) of the cerebral ganglion contribute to food-induced arousal by enhancing the strength of buccal muscle contractions, and by modulating the output of the central pattern generator for biting movements. In order to test this hypothesis in intact, free-moving animals and to determine if the MCCs play a role in satiation of feeding, the behavior of animals that had their MCCs destroyed by intracellular injection of proteases was compared with that of B Cell-Lesion and Dye injection control animals (Experiment 1) or surgical control animals (Experiment 2). Nonfeeding behaviors such as defensive withdrawal responses, locomotion, and righting reflexes were unaffected by MCC lesioning. Also unaffected by MCC lesioning were appetitive feeding behaviors and the amount of food needed to satiate animals. Significant behavioral deficits in consummatory feeding behaviors, which remained stable for periods exceeding 10 d, were observed in the MCC-lesioned animals but not in controls. Lesioned animals exhibited a slowing of rate of repetitive biting responses by 40% of controls and had reduced magnitudes of repetitive bites, particularly at the end of a testing run of 10 consecutive bites. The deficit in bite magnitude was minimally evident in food-deprived animals (Experiment 1) but became more pronounced as animals were fed to satiation (Experiment 2). MCC-lesioned animals still exhibited a residual build-up of the rate and magnitude of biting responses at the onset of feeding behavior. This suggests that, in addition to the MCCs, there are other sources of modulation that contribute to plasticity of consummatory responses during the food-induced arousal state.

Effect of CCK antibodies on food intake and weight gain in zucker rats

While exogenous administration of cholecystokinin (CCK) decreases food intake in many species, it has not been demonstrated conclusively that CCK is necessary for satiety to occur. In these experiments the role of CCK in eliciting satiety was further investigated by using endogenously produced and exogenously administered antibodies to CCK which were hypothesized to sequester circulating CCK. In the first experiment Zucker obese (n=12, 192±16 g) and lean (n=12, 152±11 g) male rats were administered CCK-8 conjugated to bovine serum albumin or bovine serum albumin by subcutaneous administration in Freund's adjuvant. Average percent binding of 125I-gastrin-17 by serum taken 4, 8 and 12 weeks after treatment initiation was increased (19.9 vs. 2.1, p<0.001) in rats treated with CCK conjugate than controls, and the increase was greater in lean (27.5 vs. 1.9) than in obese (12.2 vs. 2.2, p<0.001) rats. In lean, but not obese rats, average daily food intake and weight gain were increased (9 and 17% p<0.04 and p<0.02 respectively) in rats with CCK-AB compared with rats with no CCK-AB during the three months. Development of CCK-AB did not affect food intake response to exogenously administered CCK-8 or pancreas weight relative to body weight. In Experiment 2 increased food intakes of obese and lean rats 30 min after intraperitoneal injection of rabbit serum with CCK-AB were greater than those after intraperitoneal injection of rabbit serum without CCK-AB (1.92 vs. 1.41, g, p<0.007). Percent binding of serum from rats administered the same rabbit serum with CCK-AB intraperitoneally increased after 30 min (2.29 vs. 0.97, p<0.05). Thus, increased food intake may have been due to sequestering of free circulating CCK by the absorbed CCK-AB. In these experiments it is postulated that sequestering of CCK released during a meal increased the size of that meal; and in rats which developed endogenous CCK-AB, daily food intake and weight gain were increased, providing strong evidence that CCK plays a physiological role in satiety. The lack of response in obese rats with CCK-AB may be related to their decreased sensitivity to the effects of CCK on food intake and pancreas exocrine function.

Cholecystokinin in the central nervous system: A minireview

This review focuses on the structure, distribution, neuronal pathways, receptor binding, release, biosynthesis and degradation of CCK in the central nervous system. Other aspects of the isolation and chemistry of CCK (1), its role in satiety (2), as a hormone or neurotransmitter (3,4), and its evolution (5) have been reviewed recently.

Hormones and feed intake.

During the several decades that hormones have been considered for roles in the control of feeding, certain ones have gained special attention, although the role assigned to any one hormone has varied from time to time. Three classes of hormones have been considered in this review: gastrointestinal, brain, and pancreatic. Of these classes, two have obtained the most compelling evidence for a physiological role in the control of feeding. CCK, an intestinal and brain hormone, appears to be involved in satiety. Glucagon of pancreatic origin appears also to play an important role in satiety. These hormones, when sequestered by a specific antibody, cause a delay in satiety and thus increase food intake. Insulin, another pancreatic hormone, has been considered for several roles in the control of feeding. Recently, attention has been given to the possibility that insulin of the CSF provides an integrated link between the metabolic state of the adipose tissue and the brain structures concerned with the control of feeding. Thus, insulin may be a primary hormone involved in the maintenance of energy balance or of body-weight. Finally, brain opiate peptides, e.g. dynorphin, are very likely involved in the transmission of information concerned with the interaction of feeding and maintenance of energy balance. Clearly, hormones play primary roles in the control of feeding behaviour and the regulation of energy balance, but much remains to be done to establish their specific actions or components of the associated physiological systems.

Peptides with CCK-like activity administered intracranially elicit satiety in sheep

Cholecystokinin (CCK) peptides and receptors have been shown to be present in the brain as well as in gastrointestinal organs. While functions for peripheral CCK are well recognized, those for central CCK peptides are only now being investigated. We have shown previously that CCK-octapeptide (CCK-OP) is a very potent and specific suppressor of feeding when administered in the cerebral ventricles of sheep. In the present study the objective was to determine the relative potency of several CCK analogues in inhibiting feeding when administered as 75 min continuous injections into the lateral cerebral ventricles of 2-hr fasted sheep. In comparing feeding response during CCK-OP injections to that during caerulein injections, it was found that feed intakes were similar only at an equal molar dose (0.638 pmole/min); whereas three times as much CCK-33 (1.91 pmoles/min) as CCK-OP (0.638 pmoles/min) was required to produce similar feed intakes. Both caerulein (0.638 pmoles/min) and CCK-33 (1.91 pmoles/min) caused significant decreases in feeding compared to control (sCSF). Desulfated CCK-OP had no effect on feeding at a dose (0.638 pmoles/min) that causes 80–100% decreases in feeding when the C-7 tyrosine is sulfated. Feed intake was significantly less with 2.55 pmoles/min CCK-OP than with an equal dose of desulfated CCK-OP. These results concur with those of previous studies on specific CCK receptors in the pancreas and in the brain, and therefore support the concept of specific CCK receptors in brain having a role in satiety.

Feeding elicited by injection of the cholecystokinin antagonist dibutyryl cyclic GMP into the cerebral ventricles of sheep

Dibutyryl cyclic GMP (Bt 2cGMP) is a specific competitive antagonist of the action of cholecystokinin (CCK) on dispersed pancreatic acini and on gall bladder smooth muscle, and it exerts its effects at the CCK receptor level. CCK peptides in brain are proposed to have a role in satiety, and because (1) brain CCK receptors have characteristics similar to those of peripheral CCK receptors, and (2) injections of CCK-octapeptide (CCK-OP) into the cerebrospinal fluid (CSF) of sheep decreased feeding, we tested the ability of Bt 2cGMP to inhibit satiety when injected into the cerebral ventricles of sheep. Feed intakes were increased by more than 150% during the first hour of a two hour continuous injection of 2.9 nmole/min Bt 2cGMP (N=20, p<0.05). Although 29 and 290 nmoles/min Bt 2cGMP caused agitation and no increase in feeding, only normal behaviors were observed with the 2.9 nmole/min dose. A lower dose (0.72 nmole/min) had no effect on behavior or feed intake. The increase in feed intake caused by injection of 2.9 nmole/min Bt 2cGMP into the cerebral ventricles suggests that this nucleotide, acting as an antagonist of CNS CCK receptors, inhibited satiety and thus elicited feeding. These results, in conjunction with those demonstrating an increase in feeding following the binding of CCK in CSF by CCK antibody, support the hypothesis that brain CCK is released during feeding and acts on CCK receptors which are involved in the control of feed intake.

Effets du repas sur l'agrément d'odeurs alimentaires et nonalimentaires chez l'homme

Food-related and nonfood-related olfactory stimuli were presented to human subjects before and after they ate a meal. The subjects were asked to judge the pleasantness or the unpleasantness of the stimuli using a category scale. The responses of ten control subjects, who remained fasted, did not change during a 120 min period. With the other subjects on ad lib meals there followed these two characteristic phenomena: (1) there was a significant drop in the pleasantness of the food-related odors (negative alliesthesia); and, (2) there was no change in the pleasantness of the non-food-related odors (no alliesthesia). Therefore negative alliesthesia is specific to food-related odors. Negative alliesthesia reached a maximum within 60 min after the meals, then decreased and disappeared within the next 60 min. In three other subjects, with abnormal body weight, negative alliesthesia did not occur after the meal. These results favor the view that olfactory alliesthesia plays a role in satiety and the control of intermeal interval. They are also compatible with the existence of a ponderostat.