Skin electrical activity of the stomach and intestine during long-term antiorthostatic hypokinesia

The skin electrical activity of the gastrointestinal tract in the stomach and small intestine frequency ranges was studied for four months in 13 men under the conditions of antiorthostatic hypokinesia (AOH). On an empty stomach, both the gastric and small intestine electrical activities increased to a level comparable with that of the increase detectable after eating under the conditions of normal motor activity, whereas the response to food stimulation was inhibited. The ratios between the parameters of spectral analysis testified to a higher tonic component in the stomach and a higher peristaltic component in the intestine under the conditions of AOH. The observed changes in the gastric and intestinal electrical activities were observed against a background of a hypersecretory state of the stomach and an increase in the intestinal contents. During the readaptation period, both the gastric and intestinal electrical activities increased significantly, whereas the response to food stimulation was inhibited.     

Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

Intraperitoneal injection of CCK reduces food intake and triggers a behavioral pattern similar to natural satiation. Reduction of food intake by CCK is mediated by vagal afferents that innervate the stomach and small intestine. These afferents synapse in the hindbrain nucleus of the solitary tract (NTS) where gastrointestinal satiation signals are processed. Previously, we demonstrated that intraperitoneal (IP) administration of either competitive or noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists attenuates reduction of food intake by CCK. However, because vagal afferents themselves express NMDA receptors at both central and peripheral endings, our results did not speak to the question of whether NMDA receptors in the brain play an essential role in reduction of feeding by CCK. We hypothesized that activation of NMDA receptors in the NTS is necessary for reduction of food intake by CCK. To test this hypothesis, we measured food intake following IP CCK, subsequent to NMDA receptor antagonist injections into the fourth ventricle, directly into the NTS or subcutaneously. We found that either fourth-ventricle or NTS injection of the noncompetitive NMDA receptor antagonist MK-801 was sufficient to inhibit CCK-induced reduction of feeding, while the same antagonist doses injected subcutaneously did not. Similarly fourth ventricle injection of d-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphoric acid (d-CPPene), a competitive NMDA receptor antagonist, also blocked reduction of food intake following IP CCK. Finally, d-CPPene injected into the fourth ventricle attenuated CCK-induced expression of nuclear c-Fos immunoreactivity in the dorsal vagal complex. We conclude that activation of NMDA receptors in the hindbrain is necessary for the reduction of food intake by CCK. Hindbrain NMDA receptors could comprise a critical avenue for control and modulation of satiation signals to influence food intake and energy balance.     

Gastric Electrical‐Stimulation Effects on Canine Gastric Emptying,Food Intake,and Body Weight

Objective: It has been reported that electrical stimulation at the distal stomach can disrupt intrinsic gastric electrical activity and delay gastric emptying. Gastric dysrhythmia and impaired gastric emptying are associated with upper gastrointestinal symptoms and weight loss. The purpose of this study was to evaluate the effect of low‐frequency/long‐pulse gastric electrical stimulation (GES), at proximal and distal stomach, on canine gastric emptying, food intake, and body weight. Research Methods and Procedures: Eight dogs were surgically implanted with four pairs of electrodes along the greater curvature and a gastric tube at the dependent part of the stomach. Liquid gastric emptying at baseline, during proximal and distal GES at 6 cycles per minute, was assessed first by a dye dilution technique. Proximal and distal GES were then randomly delivered during feeding for 10 consecutive days, and food intake and body weight were recorded daily. Results: There was no significant difference in gastric emptying parameters among the various sessions. The mean daily food consumption was significantly reduced during both sessions of GES, resulting in significant immediate weight loss. Percentage weight loss was comparable between both sessions of GES. Discussion: Short‐term GES significantly reduced canine food intake and weight. This effect may not be related to changes in gastric emptying. GES may have a potential role in the treatment of obesity.     

The pacemaker activity of interstitial cells of Cajal and gastric electrical activity

Interstitial cells of Cajal (ICC) are the pacemaker cells in the gut. They have special properties that make them unique in their ability to generate and propagate slow waves in gastrointestinal muscles. The electrical slow wave activity determines the characteristic frequency of phasic contractions of the stomach, intestine and colon. Slow waves also determine the direction and velocity of propagation of peristaltic activity, in concert with the enteric nervous system. Characterization of receptors and ion channels in the ICC membrane is under way, and manipulation of slow wave activity markedly alters the movement of contents through the gut. Gastric myoelectrical slow wave activity produced by pacemaker cells (ICC) can be reflected by electrogastrography (EGG). Electrogastrography is a perspective non-invasive method that can detect gastric dysrhythmias associated with symptoms of nausea or delayed gastric emptying.     

The influence of stomach distention on feeding in the nudibranch mollusk Melibe leonina

Although research on satiation has revealed much about the effect of sensory inputs on motivational state, we have yet to fully understand exactly how satiating signals influence the neural circuits underlying specific behaviors. One organism that is well suited for addressing this question is the nudibranch Melibe leonina, because its feeding activity is easily quantified, it has translucent skin that makes the stomach easy to observe, and it has large, identifiable neurons that are very suitable for subsequent analysis of the neural correlates of satiation. In this study our goal was to document the time course of satiation in Melibe, and determine if stomach distention contributes to satiation. When exposed to brine shrimp (Artemia), Melibe immediately commenced stereotypic oral hood movements to capture prey, and continued to do so for approximately five hours. Individuals eventually stopped, despite the continued presence of food, and the slowing and eventual termination of oral hood closures was correlated with distension of the stomach caused by the ingested Artemia. We obtained further evidence that stomach distension is one of the underlying causes of satiation by injecting artificial non-nutritive food into the stomach, and by cutting open part of the stomach wall to prevent it from filling and distending. The first treatment caused satiation to occur more rapidly, while the second treatment delayed satiation. Both results demonstrate that in Melibe stomach distention has a major impact on the motivation to feed. These findings provide the framework for subsequent studies designed to determine precisely how stomach distention influences feeding circuits.     

Retrograde Gastric Electrical Stimulation Reduces Food Intake and Weight in Obese Rats

Objective: To investigate the therapeutic potential of retrograde gastric electrical stimulation (RGES) for obesity in a rodent model of obesity. Research Methods and Procedures: The study was performed in 12 obese Zucker rats implanted with two pairs of gastric serosal electrodes, one pair for stimulation and the other for recording intrinsic gastric myoelectrical activity. It was composed of an acute study in three sessions to study the effect of RGES on intrinsic gastric myoelectrical activity and acute food intake and a chronic phase to study the short‐term effect of RGES on weight. RGES was performed through the distal stomach using long pulses at a frequency of tachygastria (known to induce gastric hypomotility). Results: RGES completely entrained intrinsic gastric myoelectrical activity and turned it into tachygastria at a certain strength. RGES reduced acute food intake compared with the control (p < 0.01). A 2‐week treatment of RGES resulted in a significant reduction in food intake (p = 0.002) and a significantly greater weight loss than sham stimulation (p = 0.004). Discussion: RGES at a tachygastrial frequency reduces food intake and results in weight loss in obese Zucker rats, and its effect is probably attributed to the introduction of tachygastria in the stomach.     

Resting membrane potentials of pacemaker and non pacemaker areas in rat uterus

Microelectrode studies of pacemaker and non pacemaker cells in pregnant rat uterus have shown the pacemaker areas to have a constant value of RMP throughout pregnancy which was always significantly smaller than that of non pacemaker cells. The development of new pacemaker areas was associated with membrane depolarization. A number of agents and conditions which caused membrane depolarization also induced pacemaker activity in previously non pacemaker areas but did so at different levels of membrane depolarization. Potassium depolarization failed to induce pacemaker activity. It is concluded that a low level of RMP is an important factor but not sufficient alone to explain the occurence of pacemaker activity.The resting membrane potentials (RMP) of spontaneously active smooth muscles are appreciably smaller than those of nonspontaneously active muscles (3) and comparable in magnitude to those of other tissues showing spontaneous activity such as the frog sinus venosus(7), rabbit sino-auricular node (10) and embryonic heart muscle (6). In intestinal smooth muscle, where all cells appear to be spontaneously active, a clear relationship can be demonstrated between fluctuating levels of RMP and the incidence of action potential activity, and the ionic and metabolic basis of slow wave activity has been extensively investigated (5, 8). In other smooth muscles, such as the ureter and uterus, where electrical activity arises from pacemaker areas (11, 12), the underlying causes of spontaneous activity are less well understood and the relationships between pacemaker activity, RMP and excitability have not been clearly defined. As an initial approach to studying this problem we have chosen to investigate the relationship between RMP and pacemaker activity in the uterus of the pregnant rat.     

Solving post-prandial reduction in performance by adaptive regurgitation in a freshwater fish

Foraging animals must balance benefits of food acquisition with costs induced by a post-prandial reduction in performance. Eating to satiation can lead to a reduction in locomotor and escape performance, which increases risk should a threat subsequently arises, but limiting feeding behaviour may be maladaptive if food intake is unnecessarily reduced in the prediction of threats that do not arise. The efficacy of the trade-off between continued and interrupted feeding therefore relies on information about the future risk, which is imperfect. Here, we find that black carp (Mylopharyngodon piceus) can balance this trade-off using an a posteriori strategy; by eating to satiation but regurgitating already ingested food when a threat arises. While degrees of satiation (DS) equal to or greater than 60% reduce elements of escape performance (turning angle, angular velocity, distance moved, linear velocity), at 40% DS or lower, performance in these tasks approaches levels comparable to that at 0% satiation. After experiencing a chasing event, we find that fish are able to regurgitate already ingested food, thereby changing the amount of food in their gastrointestinal tract to consistent levels that maintain high escape performance. Remarkably, regurgitation results in degrees of satiation between 40 and 60% DS, regardless of whether they had previously fed to 40, 60 or 100% DS. Using this response, fish are able to maximize food intake, but regurgitate extra food to maintain escape performance when they encounter a threat. This novel strategy may be effective for continual grazers and species with imperfect information about the level of threat in their environment.     

Increased short-term food satiation and sensitivity to cholecystokinin in neurotrophin-4 knock-in mice

Neurotrophin-4 (NT-4) knockout mice exhibited decreased innervation of the small intestine by vagal intraganglionic laminar endings (IGLEs) and reduced food satiation. Recent findings suggested this innervation was increased in NT-4 knock-in (NT-4KI) mice. Therefore, to further investigate the relationship between intestinal IGLEs and satiation, meal patterns were characterized using solid and liquid diets, and cholecystokinin (CCK) effects on 30-min solid diet intake were examined in NT-4KI and wild-type mice. NT-4KI mice consuming the solid diet exhibited reduced meal size, suggesting increased satiation. However, compensation occurred through increased meal frequency, maintaining daily food intake and body weight gain similar to controls. Mutants fed the liquid diet displayed a decrease in intake rate, again implying increased satiation, but meal duration increased, which led to an increase in meal size. This was compensated for by decreased meal frequency, resulting in similar daily food intake and weight gain as controls. Importantly, these alterations in NT-4KI mice were opposite, or different, from those of NT-4 knockout mice, further supporting the hypothesis that they are specific to vagal afferent signaling. CCK suppressed short-term intake in mutants and controls, but the mutants exhibited larger suppressions at lower doses, implying they were more sensitive to CCK. Moreover, devazepide prevented this suppression, indicating this increased sensitivity was mediated by CCK-1 receptors. These results suggest that the NT-4 gene knock-in, probably involving increased intestinal IGLE innervation, altered short-term feeding, in particular by enhancing satiation and sensitivity to CCK, whereas long-term control of daily intake and body weight was unaffected.     

Effect of Alginate on Satiation,Appetite, Gastric Function,and Selected Gut Satiety Hormones in Overweight and Obesity

Lack of control of food intake, excess size, and frequency of meals are critical to the development of obesity. The stomach signals satiation postprandially and may play an important role in control of calorie intake. Sodium alginate (based on brown seaweed Laminaria digitata) is currently marketed as a weight loss supplement, but its effects on gastric motor functions and satiation are unknown. We evaluated effects of 10 days treatment with alginate or placebo on gastric functions, satiation, appetite, and gut hormones associated with satiety in overweight or obese adults. We conducted a randomized, 1:1, placebo‐controlled, allocation‐concealed study in 48 overweight or obese participants with excluded psychiatric comorbidity and binge eating disorder. All underwent measurements of gastric emptying (GE), fasting, and postprandial gastric volumes (GVs), postprandial satiation, calorie intake at a free choice meal and selected gut hormones after 1 week of alginate (three capsules vs. matching placebo per day, ingested 30 min before the main meal). Six capsules were ingested with water 30 min before the GE, GV, and satiation tests on days 8–10. There were no treatment group effects on GE or volumes, gut hormones (ghrelin, cholecystokinin (CCK), glucagon‐like peptide‐1 (GLP‐1), peptide YY (PYY)), satiation, total and macronutrient calorie intake at a free choice meal. There was no difference detected in results between obese and overweight patients. Alginate treatment for a period of 10 days showed no effect on gastric motor functions, satiation, appetite, or gut hormones. These results question the use of short‐term alginate treatment for weight loss.     

Working for food shifts nocturnal mouse activity into the day

Nocturnal rodents show diurnal food anticipatory activity when food access is restricted to a few hours in daytime. Timed food access also results in reduced food intake, but the role of food intake in circadian organization per se has not been described. By simulating natural food shortage in mice that work for food we show that reduced food intake alone shifts the activity phase from the night into the day and eventually causes nocturnal torpor (natural hypothermia). Release into continuous darkness with ad libitum food, elicits immediate reversal of activity to the previous nocturnal phase, indicating that the classical circadian pacemaker maintained its phase to the light-dark cycle. This flexibility in behavioral timing would allow mice to exploit the diurnal temporal niche while minimizing energy expenditure under poor feeding conditions in nature. This study reveals an intimate link between metabolism and mammalian circadian organization.     

Gastric Motor and Sensory Functions in Obesity

In the vast majority of affected individuals, obesity involves overconsumption of food relative to calorie requirements. The sensory function of the stomach may play a key role in the cessation of food ingestion. This sensation of the stomach is, in part, determined by its motor functions, such as tone and compliance and the rate of emptying. However, studies of gastric emptying in normal‐weight and obese persons have shown inconsistent results. Gastric capacity was larger in obese persons when tested with an intragastric latex balloon filled with water. In contrast, other studies using the barostat or imaging (single‐photon emission computed tomography) techniques reported no differences in gastric volume or compliance between obese and lean subjects. On the other hand, increased body mass and fasting gastric volume are independently associated with delayed satiation under standard laboratory conditions of food ingestion. These data suggest that changes in gastric motor and sensory functions in obesity may present useful targets to prevent and treat obesity. Further well‐controlled, validated studies are needed to clarify the potential role of altering the stomach's function as a means of controlling food intake in obesity.     

Leptin effect in ob/ob mice under thermoneutral conditions depends not necessarily on central satiation

Energy expenditure in ob/ob mice kept at thermoneutrality was quantified from food intake and body composition of mice treated with leptin over 15 and 75 days, respectively. Energy expenditure in response to 15 days of treatment with leptin was twice as high as under pair-feeding conditions, indicating extensive breakdown of adipose tissue independent of a centrally mediated satiation. Leptin-induced reduction of food intake ceased during treatment with leptin over 75 days, when the lipid reserves of the mice were depleted and energy expenditure became similar to that in lean mice. Energy mobilized in leptin-treated ob/ob mice from endogenous lipid resources and similar to the food energy consumed in hyperphagic ob/ob controls may cause satiation. Maximal energy expenditure in both groups may correspond to their energy supply: energy expenditure in ob/ob mice was shown to be correlated to the food intake in the absence of leptin. Leptin effects observed in ob/ob mice under thermoneutral conditions may modify the traditional view of the functionality of the hormone.     

Motivation dependence of brain self-stimulation in the pigeon

Several brain sites in the pigeon were identified as maintaining electrical brain self-stimulation. Depending on the site, stimulus currents yielding maximal responding varied from 20 to 160 μA. A high proportion of the sites only yielded self-stimulation behaviour if the subjects were deprived of food; when the birds were at full weight there was only one site at which the stimulation continued to be rewarding. Some, but weak, evidence of stimulus satiation was found. Overt behaviour elicited by non-contingent stimulation did not correlate with the reinforcing or neutral nature of the sites tested. While some positive sites were associated with structures known to be involved in the control of feeding, others were not. The hypothesis that stimulation at the hunger-dependent sites might have elicited temporary satiation signals is considered.     

EEG-correlates of alimentary behavior in rabbits with different levels of hunger and satiety]

The electrical activity of the rabbit brain at different stages of hunger and satiation was correlated with the animal's behavioral reactions. It has been found that alimentary reactions are attended with the appearance of complex high-amplitude and high-frequency electrical potentials in the lateral hypothalamic area, which increased with the longer duration of the animal's hunger, as well as during search, in response to natural and conditioned alimentary stimuli, and when feeding. As satiation sets in, they fade and disappear after food refusal. It is assumed that this form of activity is an EEG expression of alimentary motivational excitation. Its constituent rhythms reflect the different components of alimentary excitation.     

Effect of experimental conditions on the stomach evacuation of Coregonus lavaretus L.

The gastric evacuation of juveniles of Coregonus lavaretus L. fed on living Daphnia pulicaria was investigated. Three successive stages of stomach evacuation were observed when one meal per day was given: (i) a lag phase between the end of food intake and the beginning of stomach evacuation, (ii) a linear reduction of stomach content, (iii) a long residence time for food relics in the stomach. The initial stomach content and the stomach evacuation time are correlated positively. The stomach content increased during feeding when three meals day ⁻¹ were provided and it decreased when no food was available. During the course of an experiment the highest stomach content found increased with increasing daly ration. Excess feeding resulted in a low stomach content similar to that found with rations about 30–50% of the maximum daily food intake. Therefore the daily food intake cannot be determined by the single parameter of stomach content alone. Identical initial stomach contents showed significantly higher stomach evacuation rates under three meals day⁻¹ conditions than under one meal day⁻¹ conditions.     

Fibre-induced feed sorting in King Quail (Coturnix chinensis): behavioural plasticity elicited by a physiological challenge

We examined the effect of an abrupt change in diet fibre content on the feed intake, gastrointestinal morphology and utilisation of gastroliths by a small (ca. 40 g body mass) herbivorous bird, the King Quail (Coturnix chinensis). King Quail were acclimated for 14 days on a low-fibre (LF) pullet starter diet. Following acclimation, half the quail population was immediately switched to a 23 % wood-shaving diluted high-fibre (HF) diet for a further 14 days. Contrary to expectations, we found no differences in feed intake, gut morphology or gastrolith mass between the LF- and HF-fed quail. However, when switched from the LF to HF diet, the quail commenced feed-sorting behaviours that permitted HF-fed animals to maintain body condition (mass, abdominal fat mass) without adjustments to intestinal organ sizes or gastrolith mass. Feed sorting was initiated only after exposure to the HF diet, which corresponded with an immediate reduction in food intake, suggesting that the sorting behaviour was cued by a physiological challenge associated with the HF diet. This challenge apparently induced preferential sorting behaviour and was possibly due to abrupt changes in the rate of food passage, impacting satiation or other internal cues.     

Neural regulation of slow-wave frequency in the murine gastric antrum

Gastric peristaltic contractions are driven by electrical slow waves modulated by neural and humoral inputs. Excitatory neural input comes primarily from cholinergic motor neurons, but ACh causes depolarization and chronotropic effects that might disrupt the normal proximal-to-distal spread of gastric slow waves. We used intracellular electrical recording techniques to study cholinergic responses in stomach tissues from wild-type and W/W(V) mice. Electrical field stimulation (5 Hz) enhanced slow-wave frequency. These effects were abolished by atropine and the muscarinic M(3)-receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide. ACh released from nerves did not depolarize antral muscles. At higher rates of stimulation (10 Hz), chronotropic effects were mediated by ACh and a noncholinergic transmitter and blocked by muscarinic antagonists and neurokinin (NK(1) and NK(2))-receptor antagonists. Neostigmine enhanced slow-wave frequency, suggesting that the frequency of antral pacemakers is kept low by efficient metabolism of ACh. Neostigmine had no effect on slow-wave frequency in muscles of W/W(v) mice, which lack intramuscular interstitial cells of Cajal (ICC-IM). These muscles also showed no significant chronotropic response to 5-Hz electrical field stimulation or the cholinergic agonist carbachol. The data suggest that the chronotropic effects of cholinergic nerve stimulation occur via ICC-IM in the murine stomach. The capacity of gastric muscles to metabolize ACh released from enteric motor neurons contributes to the maintenance of the proximal-to-distal slow-wave frequency gradient in the murine stomach. ICC-IM play a critical role in neural regulation of gastric motility, and ICC-IM become the dominant pacemaker cells during sustained cholinergic drive.     

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

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.     

Attenuated satiation response to intestinal nutrients in rats that do not express CCK-A receptors.

Pharmacological experiments suggest that satiation associated with intestinal infusion of several nutrients is mediated by CCK-A receptors. Otsuka Long-Evans Tokushima Fatty, (OLETF), rats do not express CCK-A receptors and are insensitive to the satiation-producing effects of exogenous CCK. To further evaluate the role of CCK-A receptors in satiation by intestinal nutrient infusion, we examined intake of solid (pelleted rat chow) or liquid (12.5% glucose) food intake, following intestinal infusions of fats (oleic acid or fat emulsion), sugars (maltotriose or glucose), or peptone in OLETF rats and Long Evans Tokushima Otsuka control rats (LETO). Intestinal infusion of glucose or maltotriose reduced solid food intake more in LETO than in OLETF rats from 30 min through 4 h post infusion. Reduction of solid food intake by intestinal infusions of fat or peptone did not differ between OLETF and LETO rats during the first 30 min post infusion, but reduction of intake by these infusates was attenuated in OLETF rats over the ensuing 4h post infusion. Intestinal infusion of glucose, oleate, fat emulsion and peptone reduced 30-min intake of 12.5% glucose more in LETO than OLETF rats. Furthermore, pretreatment with the CCK-A receptor antagonist, devazepide, attenuated intestinal nutrient-induced reduction of food intake only in LETO, but not OLETF rats. Our results confirm pharmacological results, indicating that CCK-A receptors participate in satiation by nutrients that elevate plasma CCK concentrations, as well as by nutrients that do not stimulate secretion of endocrine CCK. In addition, our results indicate: 1) that OLETF rats have deficits in the satiation response to a variety of intestinal nutrient infusions; 2) that the temporal pattern for CCK-A receptor participation in satiation by intestinal nutrients is different during ingestion of liquid and solid foods and 3) that intestinal nutrients provide some satiation signals that are CCK-A receptor mediated and some that are not.