Effects of cholecystokinin-octapeptide (CCK-8) on food intake and gastric emptying in man

Food intake and gastric emptying were measured simultaneously after cholecystokinin-octapeptide (CCK-8) and saline infusions in order to test the hypothesis that reduction in gastric emptying mediates the effect of CCK-8 on food intake. Each of twelve nonobese healthy men received intravenous infusions of CCK-8 and saline on separate nonconsecutive days after they had consumed 500 g of tomato soup tagged with technetium-99-DTPA. Intake of a test meal was measured 20 min after consumption of the soup while gastric emptying was simultaneously monitored by gamma emission scintigraphy of the soup. Food intake and gastric emptying of the soup were both significantly reduced by CCK-8 infusions in comparison to saline. There was a significant correlation between the amount of the test meal eaten and the amount of soup emptied during the period the test meal was being eaten, but not before the meal, only on days when CCK-8 was infused. Differences in intakes between days when saline was infused and days when CCK-8 was infused did not correlate with differences in gastric emptying of soup. These results suggest that CCK may amplify signals of satiety in proportion to the fullness of the stomach. Gastric emptying per se may not mediate the effects of CCK-8 on food intake.     

Volume and variety: relative effects on food intake

Volume has been shown to be an important direct control of food intake, since larger volumes of food consumed prior to a meal can inhibit subsequent intake. Variety of food is known to stimulate food intake. The present study was designed to examine the relative effects of manipulating the volume of a soup preload in the context of providing either a single or a variety of sandwich fillings. Thirty participants (15 females; 15 males) attended the laboratory on 4 occasions to receive a low (f=240 ml, 3.6 kJ/g; m=300 ml, 3.6 kJ/g) or high (f=480 ml, 1.8 kJ/g; m=600 ml, 1.8 kJ/g) volume tomato soup preload 30 min before a sandwich lunch with either single or a variety of fillings. Overall, subjects reported significant differences in hunger and fullness as a function of volume manipulations but the satiety quotient (SQ: change in ratings divided by weight of soup) calculated just before lunch indicated a smaller SQ for high than for the low volume soup. Therefore, although subjective ratings were influenced by volume this was not sufficient to affect intake at lunch. Variety (2344+/-200 kJ) increased food intake at lunch compared to the single filling condition (2062+/-171 kJ), an enhancement by variety of 14%. In conclusion, lowering energy density and increasing volume by adding water failed to reduce intake at lunch. Clearly volume effects on intake rely both on amount consumed and energy density. As predicted, variety stimulated food intake and this occurred across volume conditions.     

Cholecystokinin satiety and orosensory feedback

Cholecystokinin octapeptide (1.5 μg/kg CCK) was effective in reducing the number of bar-press responses for food reward. However, during the extinction session when a food pellet did not follow the bar-press, CCK was not effective in reducing the number of responses. Since the number of bar-presses during extinction is known to be positively related to the duration of food deprivation we concluded that CCK by itself did not reduce the hunger drive or the state of arousal related to food deprivation. The orosensory feedback from food intake was regarded to be a crucial element in the effect of CCK to promote satiety. It might be that food intake was needed to test the new state of satiety induced by CCK and thus without food intake during the extinction session the effect of CCK was not shown. We think that CCK may be characterized as a satiety inducer but probably not a hunger reducer. An attempt to introduce a limited amount of orosensory feedback during the extinction session was not successful in restoring the effect of CCK to suppress the food related operant response probably due to lack of proper temporal relationship between the CCK injection and the limited orosensory stimulation introduced.     

Devazepide fails to reverse the inhibitory effect of interleukin-1beta on food intake in female rats

Proinflammatory cytokines released during the course of infection elicit numerous behavioral and metabolic changes. The decrease in food intake that accompanies infection is mediated in part by interleukin-1 (IL-1). Cholecystokinin (CCK) is a neuropeptide released during a meal, decreases food intake, and previous research suggests that CCK mediates the anorectic action of IL-1. The effects of estrogen on food intake are also thought to involve CCK, as the satiety action of CCK is increased by estradiol in both intact and ovariectomized rats. Estradiol also modulates many of the behavioral and physiological effects of IL-1. The present experiment examined the ability of the CCK(A) receptor antagonist devazepide to block the effects of IL-1 and estradiol on food intake in female rats. Adult animals were ovariectomized and given two daily subcutaneous injections of estradiol benzoate (EB; 5.0 microg) or the oil vehicle 3 weeks after surgery. Three days after treatment onset, animals were pretreated with devazepide or its vehicle 30 min prior to intraperitoneal injections of IL-1beta (4.0 microg/kg) or saline given 1 h before light offset. Food and water intake was measured following 2 h of spontaneous feeding. The results indicate that devazepide failed to reverse the anorectic action of IL-1beta, although the effects of estradiol on food intake were blocked by devazepide. These data do not support a role for CCK in IL-1-induced anorexia, and suggest that cytokines may act directly on neural systems involved in the control of food intake.     

破坏大鼠极后区对胆囊收缩素抑制摄食跑速作用的影响

胆囊收缩素(CCK)能抑制大鼠的摄食量和摄食跑速。本文向腹腔内注入CCK(10μg/kg)后15分钟内发现大鼠的摄食量和在迷宫内的摄食跑速都明显降低。破坏大鼠的极后区后,向腹腔内注入等量的CCK,则CCK抑制摄食作用明显减弱,开始的15分钟内摄食量显著增多,摄食跑速明显加快。提示大鼠的极后区在CCK引起的摄食抑制作用中起重要作用,极后区可能是CCK在脑干内的一个重要的感受器。在破坏了极后区同时又破坏了孤束核的动物,亦有降低CCK抑制摄食的作用。但与正常大鼠对照组比较,破坏极后区的大鼠摄食量减少,而摄食跑速没有明显差别。     

Plasticity in vagal afferent neurones during feeding and fasting: mechanisms and significance

The ingestion of food activates mechanisms leading to inhibition of food intake and gastric emptying mediated by the release of regulatory peptides, for example cholecystokinin (CCK), and lipid amides, e.g. oleylethanolamide from the gut. In addition, there are both peptides (e.g. ghrelin) and lipid amides (e.g. anandamide) that appear to signal the absence of food in the gut and that are associated with the stimulation of food intake. Vagal afferent neurones are a common target for both types of signal. Remarkably, the neurochemical phenotype of these neurones itself depends on nutritional status. CCK acting at CCK1 receptors on vagal afferent neurones stimulates expression in these neurones of Y2-receptors and the neuropeptide CART, both of which are associated with the inhibition of food intake. Conversely, in fasted rats when plasma CCK is low, these neurones express cannabinoid (CB)-1 and melanin concentrating hormone (MCH)-1 receptors, and MCH, and this is inhibited by exogenous CCK or endogenous CCK released by refeeding. The stimulation of CART expression by CCK is mediated by the activation of CREB and EGR1; ghrelin inhibits the action of CCK by promoting nuclear exclusion of CREB and leptin potentiates the action of CCK by the stimulation of EGR1 expression. Vagal afferent neurones therefore constitute a level of integration outside the CNS for nutrient-derived signals that control energy intake and that are capable of encoding recent nutrient ingestion.     

Role of cholecystokinin and its antagonist proglumide on macronutrient selection in European sea bass Dicentrarchus labrax, L

Teleost fish are able to adjust their energy intake when fed on pure macronutrient sources, although the exact mechanisms regulating macronutrient selection remain unknown. Since cholecystokinin (CCK) has been reported to modify macronutrient selection patterns in mammals, we explored the effect of CCK administered orally to European sea bass on the selection of separately encapsulated macronutrients. CCK doses of 0.05, 0.15 and 0.25 mg/kg BW administered in gelatine capsules for 5 consecutive days produced a significant inhibition of total food intake (21, 28 and 51%, respectively) at highest doses, evenly reducing the quantity of all the macronutrients ingested and, without affecting their relative proportions in the diet. Oral administration of proglumide, a non-specific CCK receptor antagonist, at doses of 5, 15 and 25 mg/kg BW, induced a quantitative total food intake increase of 2, 18 and 44%, respectively, and an increase of 52% in CH and 43% in P quantity ingested at highest dose. Co-administration of proglumide (25 mg/kg BW) and CCK (0.25 mg/kg BW) in a single preload capsule blocked the effects observed with CCK alone. In conclusion, orally administered CCK induced an anorexigenic effect on both total food and single macronutrient intake, an effect that is counteracted by the CCK antagonist proglumide.     

Multi-hormonal weight loss combinations in diet-induced obese rats: Therapeutic potential of cholecystokinin?

Cholecystokinin (CCK) acutely synergizes with amylin to suppress food intake in lean mice. To extend on these findings, the present studies sought to identify neural correlates for the interaction of amylin and CCK, as well as further understand the therapeutic potential of CCK-based combinations in obesity. First, c-Fos activation was assessed in various brain nuclei after a single intraperitoneal injection of amylin (5 µg/kg) and/or CCK (5 µg/kg). Amylin and CCK additively increased c-Fos within the area postrema (AP), predominantly in noradrenergic (e.g., dopamine-β-hydroxylase-containing) cells. Next, amylin (100 or 300 μg/kg/d) and/or CCK (100 or 300 μg/kg/d) were subcutaneously infused for 7 days in diet-induced obese (DIO) rats. Amylin treatment of DIO rats for 7 days induced significant body weight loss. CCK, while ineffective alone, significantly enhanced body weight loss when co-administered with the higher dose of amylin. Finally, the addition of CCK (300 μg/kg/d) to leptin (125 µg/kg/d), and to the combination of amylin (50 μg/kg/d) and leptin (125 μg/kg/d), was also explored in DIO rats via sustained subcutaneous infusion for 14 days. Infusion of amylin/leptin/CCK for 14 days exerted significantly greater body weight loss, inhibition of food intake, and reduction in adiposity compared to amylin/leptin treatment alone in DIO rats. However, co-infusion of CCK and leptin was an ineffective weight loss regimen in this model. Whereas CCK agonism alone is ineffective at eliciting or maintaining weight loss, it durably augmented the food intake and body weight-lowering effects of amylin and amylin/leptin in a relevant disease model, and when combined with amylin, cooperatively activated neurons within the caudal brainstem.     

The effect of cholecystokinin on food intake in gonadectomized and intact rats: the influence of sex hormones

Cholecystokinin (CCK) suppresses food intake in a number of animal models, but appears to be less effective in females [5,23]. We studied the effect of CCK on food intake in female rats on each day of the estrous cycle. In addition, we evaluated the effect of sex hormones on food intake in intact and castrate male rats which had been injected daily with oil or testosterone propionate + oil and ovariectomized female rats injected daily with oil, estradiol, progesterone or estradiol + progesterone. Food intake in intact, castrate and castrate + testosterone replaced male rats was decreased by CCK (5, 10 and 20 micrograms/kg) IP (p less than 0.05). Food intake was decreased by CCK (20 micrograms/kg) only during diestrous and metestrus in cycling female rats. During metestrus, a period of low estradiol in the presence of progesterone, food intake was also suppressed by CCK (5 and 10 micrograms/kg). CCK failed to decrease food intake in ovariectomized females receiving oil, estradiol and estradiol + progesterone. However, animals receiving progesterone alone responded to the high dose of CCK (20 micrograms/kg). Our data suggest that the effect of CCK on food intake in female rats may be dependent on the presence of progesterone. The lack of sensitivity to CCK during proestrus and estrus suggests that estradiol may be modulating the "permissive" action of progesterone on CCK's satiety effect.     

CCK,endogenous insulin condition and satiety in free-fed rats

Cholecystokinin (CCK) has been shown to elicit insulin secretion and increased insulin availability has been shown to correlate with increased satiety attributed to reduced size of spontaneously occurring meals. The present experiment, however, clearly showed that CCK was effective in suppressing food ingestion in free-fed rats independent of the animal's level of insulin. Rats were tested with 1, 2 and 4 μg/kg of CCK-octapeptide (Sincalide, Squibb) during a baseline (pancreatic-normal) period, an insulin-poor state (streptozotocin diabetic) and an insulin clamped condition (diabetic treated by a minipump). CCK produced a highly significant (p<0.01) reduction of food intake compared to saline, control injections regardless of the insulin conditions of the animals. Higher doses of CCK were more effective than lower doses during all three periods of study. CCK and hyperinsulinemia function independently if they produce satiety or reductions in food intake.     

Umami and appetite: effects of monosodium glutamate on hunger and food intake in human subjects

Subjects consumed soup (beef consomme) preloads of a fixed size containing different concentrations of monosodium L-glutamate (MSG). Effects on appetite following these preloads, and when no soup was consumed, were assessed in 3 studies. The soups supplemented with MSG were rated as more "pleasant," more "savoury" and more "satisfying" than soup with no added MSG. Compared with the no preload condition, consumption of the soups initially reduced appetitive motivational ratings and increased fullness ratings, but did not alter food intake in a test meal begun either 2 or 30 minutes later. This immediate inhibition of subjective motivation to eat was unaffected by MSG concentration. The failure of the soups to reduce subsequent food intake is presumably due to their low energy content (less than 10 kcal) and indicates that sensory stimulation alone is insufficient to reduce appetite. Indeed, the most important finding concerning MSG showed that motivation to eat recovered more rapidly following a lunchtime meal in which MSG-supplemented soup was served as the first course (compared both with the effect of unsupplemented soup and no preload). It is suggested tentatively that MSG through its stimulation of orosensory receptors and/or by improving the palatability of the soup may have influenced the metabolic disposal of nutrients consumed in the previous meal.     

Satiation due to CCK-8 derivative infusion into VMH is related to a specific macronutrient selection

Diet self-selection from carbohydrate, protein and lipid offered simultaneously was studied in adult male rats infused for 8 days with pyroglutamyl-CCK-8 (pGlu-CCK-8) (0.8 pmol/hr), a derivative of the COOH-terminal octapeptide of cholecystokinin (CCK), or vehicle bilaterally into the ventromedial hypothalamus (VMH). Infusion with pGlu-CCK-8 markedly decreased total daily energy intake mainly due to a suppressed carbohydrate intake. Both pGlu-CCK-8 and vehicle infusions caused a nonspecific decrease in protein intake, but the vehicle infusion caused a compensatory increase in lipid intake as well as carbohydrate intake, so their total energy intake was well maintained. These results suggest that the process of infusion into the VMH elicited itself a suppressive effect on protein intake, but that pGlu-CCK-8 infusion elicited a more specific suppressive effect on carbohydrate intake and, to a lesser extent, on lipid intake. These results also support the prediction that centrally administered CCK may suppress food intake and show in addition that such a suppression occurs selectively. The similarities and the differences in the patterns of macronutrient selection produced by vehicle of pGlu-CCK-8 infusions into the VMH provide further evidence of the unique functions of VMH and CCK in the feeding process.     

Role of cholecystokinin and opioid peptides in control of food intake

Of the many factors that influence food intake, there is strong evidence that opioid and CCK peptides, which stimulate feeding and elicit satiety, respectively, are important components that may act in concert to regulate energy balance. Cholecystokinin peptides have been isolated in both the brain and gastrointestinal tract, and changes in concentration in the brain and in plasma have been shown to vary with feeding. Peripherally injected CCK has been shown to elicit satiety in many species, including humans, an effect that may be mediated in the CNS via the vagus. In several species, most notably the sheep, direct injection into the CSF potently decreases food intake. Questions remaining regarding the role of CCK peptides in eliciting satiety include the sites and mechanisms of action. It is unknown whether CCK acts directly on receptors, indirectly on some other parameter, or as a neurotransmitter. Although opioid peptides have also been localized in portions of both the periphery and brain, a specific physiological role for their presence has not yet been determined. Opioid peptides from three families--endorphins, enkephalins, and dynorphins--have been shown to stimulate feeding in various species. They have been active at several opioid receptor types in the CNS, but there is limited evidence to suggest they affect food intake when administered peripherally. In contrast, peripheral injection of opiate antagonists has effectively decreased food intake, an observation that led to the original hypothesis that opioids were involved in the hunger component in the control of food intake and that excess concentrations might be involved in the development of obesity. An increasing body of evidence supports the concept that opioid and CCK peptides may interact to control food intake, but the evidence is more suggestive than conclusive.     

Food intake and selection after peripheral tryptophan

Two studies investigated the effects of peripheral (IP) administration of the dietary indispensible amino acid tryptophan, on food intake and macronutrient selection in rats adapted to a 12 hr nocturnal feeding period and a choice of 10% and 60% casein diets. In a dose-response study (35, 55, 75, 95, 115 mg/kg), the threshold dose of 75 mg/kg produced a significant reduction in total food intake (3.6 to 2.3 g, p less than 0.05) during the first hour of feeding. The reduction in carbohydrate intake (2.1 vs. 1.2 g, p less than 0.05) was greater than that for protein intake (1.6 vs. 1.1 g, p less than 0.05). Twelve hr total food intake was also decreased (20.9 to 19.5 g, p less than 0.05) and this was attributable to decreased carbohydrate intake (13.2 to 11.8 g, p less than 0.05). In a second study designed to determine if tryptophan's effects were mediated by the central nervous system, brain tryptophan uptake was blocked by co-injecting valine with tryptophan. The significant reduction in first hour total food intake by tryptophan was not prevented by co-injection of an equal quantity of valine (3.5 to 1.8 g, p less than 0.05). Again the suppression of carbohydrate intake (2.0 to 0.9 g p less than 0.05) was greater than that for protein intake (1.5 to 0.9 g, p less than 0.05). This dose of valine significantly reduced brain tryptophan uptake by 16% (21.3 to 17.8 micrograms/g, p less than 0.05) and when administered alone did not affect first hour total food intake (3.1 vs 3.2 g).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of leptin on cat intestinal vagal mechanoreceptors

Vagal afferent nerve fibres are involved in the transmission to the central nervous system of information relating to food intake and immune reactions. Leptin is involved in the control of food intake and has specific receptors in afferent vagal neurones. To investigate the role of these receptors, we studied the effects of leptin on single vagal afferent activities from intestinal mechanoreceptors in anaesthetized cats. The activity of 35 intestinal vagal mechanoreceptors was recorded by means of glass microelectrodes implanted in the nodose ganglion. Leptin (10 μg), administered into the artery irrigating the upper part of the intestine, induced activation in 17 units ( P < 0.001), inhibition in 8 units ( P < 0.05), and had no effect on 10 units. The excitatory effects of leptin were blocked by the endogenous interleukine-1β receptor antagonist, (Il-1ra, 250 μg, i.a .). Cholecystokinin (CCK, 10 μg, i.a .) induced an activatory response only in the two types of units which were responsive to leptin alone. When leptin was administered after CCK, its excitatory effects were enhanced and its inhibitory effects were blocked, whereas it had no effect on the units which were not affected by leptin alone. The interactions between leptin and CCK are specific ones, since other substances (phenylbiguanide, a serotoninergic agonist; substance P) known to activate the mechanoreceptors did not modify the effects of leptin. These results indicate that leptin appears to play a role in the control of immune responses and food intake via intestinal vagal afferent nerve fibres and that there is a functional link between leptin and Il-1β.     

The ontogeny of postingestive inhibitory stimuli: examining the role of CCK

Cholecystokinin (CCK) inhibits food intake in adults. This paper describes research examining the ability of CCK to affect feeding in infant rats and the role of CCK in the developmentally emerging ability of the rat pup to inhibit ingestion in response to sensory characteristics of food. First, data will be described from studies that asked if the CCK system is functional in preweanling rats. Specifically, these studies examined whether exogenous and endogenous CCK can decrease intake of the infant rat during independent ingestion (of a milk diet, away from the dam). In addition, the ability of exogenous CCK to activate central feeding-control areas in the brain stem and hypothalamus in infant rats was examined by C-FOS staining. Next, experiments examining which specific intake-inhibitory sensory aspects of food are mediated by CCK will be described. The volume, hypertonicity, fat, carbohydrate and protein content of a preload were separately manipulated in different studies, followed closely by a 30-min test meal. The selective CCK(1) receptor antagonist devazepide was used to assess CCK mediation of the control of intake produced by particular sensory aspects of food, at the earliest age in which this ability to control intake appears. Finally, the pattern of independent ingestion in infant OLETF rats lacking CCK(1) receptors was examined. The results suggest that the CCK intake-inhibitory mechanism is potentially available to the young, suckling pup even before it starts to feed on its own. However, it appears to mediate only a portion of the controls of intake during nursing and early stages of weaning. Some aspects of the CCK system (e.g., forebrain-hindbrain connections) and CCK's role in mediating the effects of other stimulus aspects of food apparently undergo a post-weaning maturational process.     

Trypsin inhibitor effects on food intake and weight gain in Zucker rats

Decreased body weight and increased pancreas weight which occur in rats fed raw soybeans are thought to be due to the presence of trypsin inhibitors in the soybeans (SBTI). Since trypsin is postulated to be a negative feedback signal for cholecystokinin (CCK) secretion, SBTI may have these effects by increasing secretion of CCK. CCK is a putative satiety signal; thus, increased secretion of CCK could decrease food intake, and, if maintained over a period of time, body weight. In these experiments the effects of a trypsin inhibitor [N,N-dimethyl-carbamoyl 4-(4-guanidino-benzylyloxy)-phenyl acetate methane-sulfate (DGPM)]on feeding pattern were investigated in Zucker obese and lean rats. Administration of 25-200 mg/kg DGPM to 6-hr fasted rats decreased daily food intake by dose-dependently decreasing average meal size in both obese and lean rats, but the response was greater in obese rats. Administration of 100 mg/kg DGPM twice daily for 7 days decreased food intake and body weight in obese but not lean rats. Thus, these results suggest that decreased body weight associated with SBTI is due to decreased food intake partly as a result of increased secretion of the putative satiety peptide CCK.     

The suppression of sucrose intake by cholecystokinin is scaled according to the magnitude of the orosensory control over feeding

The intestinal hormone cholecystokinin (CCK) has been shown to play a role in the termination of food intake, however its behavioral mechanism of action remains to be determined. Recent work from this laboratory suggested that the suppression of intake with CCK is dependent upon the specific orosensory characteristics of the substance being consumed and that the hormone may suppress intake by altering the behavior maintaining characteristics of orosensory stimuli. The present study further investigated this suggestion by determining whether changes in the orosensory characteristics of food alter the magnitude of the suppressive effect of CCK. Specifically, the magnitude of the CCK effect on the intake of sucrose solutions of various concentrations was determined in non-deprived rats. The results of this work indicate that the suppressive effect of synthetic CCK (CCK-8) cannot be overridden by increases in sucrose concentration. In contrast, it was found that over a range of sucrose concentrations, the magnitude of the CCK effect increased with solution concentration. Because sucrose concentration predicts both caloric density and the magnitude of orosensory control (as measured by grams consumed), it appears that CCK may act on this control to regulate meal size in proportion to the caloric density of the food.     

Stimulation of food intake and growth of swine by cholecystokinin immunization

Experimental superalimentation at 30% above ad libitum intake increased growth 40% and confirmed that voluntary food intake is a growth-limiting factor in swine. A sequence of contingent hypotheses was proposed for swine: cholecystokinin (CCK) is a regulator of food intake; food intake is enhanced by reduction of serum CCK; serum CCK is reduced by anti-CCK antibodies: anti-CCK antibodies are raised by active immunization. The objectives of this study were to determine if antibodies were raised in immunized swine and if the anti-CCK titers were sufficient to increase food intake and growth. Twelve young growing swine were immunized against cholecystokinin (CCK-8) to test the hypothesis that anticholecystokinin antibodies in serum would suppress cholecystokinin inhibition of appetite (food intake). An equal number of control animals (hSG) were immunized against the antigenic carrier protein by the same protocol. Specific binding of [125I]CCK-8, the C-terminal octapeptide, by sera diluted 1:181 increased to a peak value on day 43. Food intake and body weight gain were similar for the two groups during the first phase of the study. However, food intake was 8.2% greater and body weight gain was 10.6% greater for the CCK-8 than for the hSG group during the second phase (d 43 to d 77). Total food intake over the 77-day study was 5.4% greater for the CCK-8 group (P = .08): body weight gain was 8.3% greater (P = .006). Regression analyses confirmed that gain over the 34-day second phase increased .076 kg (P = .045; R2 = 0.34) for each percentage unit increase of serum binding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Duodenal infusion of fat, cholecystokinin secretion and satiety in the pig

The influence of the cholecystokinin (CCK) antagonist L-364,718 (0.1 mg/kg) on short-term control of food intake was studied in 6 pigs. Arterial injection of L-364,718 abolished the inhibition of intake to CCK octapeptide infusion (4 micrograms/kg/hr; from 42% p less than 0.001, to 97% of control intake), but did not alter control intake (99%). Injection of L-364,718 also abolished the inhibition of intake to duodenal infusion of emulsified fat (12 g/hr; from 76% p less than 0.001 to 105%) and of monoglyceride (24 g/hr; from 64% p less than 0.001 to 101%), but did not alter the inhibition to oleic acid (60 g/hr; 48% p less than 0.01 and 61% p less than 0.02), to glycerol (127 g/hr; 84% p less than 0.05 and 89%) or to glucose (144 g/hr; 78% p less than 0.02 and 69% p less than 0.001). These results suggest that monoglyceride-induced CCK secretion is mainly responsible for the satiety to duodenal fat in the pig, but that there is also a CCK-independent effect via the fatty acid. The results further indicate that intake of a normal barley-based diet (2% fat) is controlled via CCK-independent mechanisms.