cholecystokinin and Bulimia

The past decade has witnessed a dramatic acceleration in research on the role of the neuropeptides in the regulation of eating behavior and body weight homeostasis. This expanding research focus has been driven in part by increasing public health concerns related to obesity and the eating disorders anorexia nervosa (AN) and bulimia nervosa (BN). Preclinical advances have been facilitated by the development of new molecular and behavioral research methodologies. With a focus on clinical investigations in AN and BN, this article reviews research on selected hypothalamic and gut-related peptide systems with prominent effects on eating behavior. Studies of the orexigenic peptides neuropeptide Y and the opioid peptides have shown state-related abnormalities in patients with eating disorders. With respect to gut-related peptides, there appears to be substantial evidence for blunting in the meal-related release of the satiety promoting peptide cholecystokinin in BN. Fasting plasma levels of the orexigenic peptide ghrelin have been found to be elevated in patients with AN. As discussed in this review, additional studies will be needed to assess the role of nutritional and body weight changes in neuropeptide alterations observed in symptomatic eating disorder patients, and to identify stable trait-related abnormalities in neuropeptide regulation that persist in individuals who have recovered from an eating disorder.

Topics: Anorexia Nervosa; Bulimia; Cholecystokinin; Humans; Hypothalamus; Neural Pathways; Neuropeptides; Satiety Response

The eating disorders anorexia nervosa and bulimia nervosa are best conceptualized as syndromes and are classified on the basis of the clusters of symptoms they present. According to the multidimensional model, eating disorders begin with dieting, which is propelled into a full-blown disorder by antecedent conditions of biological vulnerability and genetics, premorbid psychological characteristics, family interactions, and social climate. The medical abnormalities present in individuals with eating disorders are due to starvation conditions and purging behaviors and will resolve with nutritional rehabilitation and the cessation of purging. Comorbid psychiatric conditions such as affective disorders, anxiety disorders, substance abuse, and personality disorders are frequently present. For anorexia nervosa, the most effective strategy is multidimensional treatment, consisting of nutritional rehabilitation, medical attention, individual cognitive psychotherapy, and family counseling or therapy if the patient is younger than age 18 years. For bulimia nervosa, the treatment of choice is cognitive-behavioral therapy with directions in a manual for therapists. A second choice for treatment is an antidepressant, beginning with fluoxetine.

Topics: Anorexia Nervosa; Bulimia; Cholecystokinin; Dopamine; Female; Humans; Neuropeptide Y; Serotonin

Normal weight bulimia nervosa, a disorder of unknown etiology, is characterized by bingeing and purging behavior, disturbances of mood, and neuroendocrine abnormalities. Bulimic women have alterations of neurotransmitter systems known to contribute to the modulation of feeding, mood, and neuroendocrine function. Bulimic patients have increased cerebrospinal fluid concentrations of peptide YY (PYY), a peptide which is a potent stimulant of feeding in experimental animals. It has been suggested that increased brain PYY activity could contribute to the powerful and uncontrollable drive of bulimic patients to binge. It also has been reported that bulimics have impaired satiety and secretion of cholecystokinin, a peptide known to induce satiety and reduce food intake in animals and humans. Most data show that bulimic women have alterations of serotonin and norepinephrine activity. In animals, serotonin appears to have effects on eating behavior (inhibition) that are opposite to the actions of endogenous norepinephrine (activation) at alpha 2 receptors in the hypothalamus. Bingeing behavior is consistent with an overactivity of the hypothalamic alpha-noradrenergic system, an underactivity of hypothalamic serotonergic systems, or a combination of both defects. In summary, it is possible that bulimic patients have a trait-related disturbance of one or more neurotransmitter systems that could cause their appetitive dysregulation. Alternatively, these neurotransmitter disturbances may be secondary to extremes of dietary intake. Nonetheless, such neurotransmitter disturbances may contribute to a high recidivism rate. That is, bulimic patients could enter a vicious cycle in which pathologic feeding sustains and provokes continued pathologic feeding behavior. Moreover, the self-reinforcing effects of bulimia, such as decreased anxiety or food craving, may be mediated through behavior-induced changes in neurotransmission.

Topics: Animals; Brain; Bulimia; Cholecystokinin; Eating; Feeding Behavior; Female; Humans; Hypothalamus; Neurotransmitter Agents; Norepinephrine; Peptide YY; Peptides; Serotonin

Topics: Anorexia Nervosa; Bulimia; Catecholamines; Cholecystokinin; Dopamine; Endorphins; Feeding and Eating Disorders; Humans

Potential mechanisms of abnormal food intake, such as dysregulation of meal-related appetite hormones, including acyl ghrelin (AG) and des-acyl ghrelin (DAG), were investigated among men and women with obesity, with and without binge eating (BE).. Participants (n = 42: 19 female, 23 male) were assigned to a liquid meal and water condition in counterbalanced order, and blood samples for measuring hormones were obtained before and after these conditions.. Participants with BE had significantly lower fasting and postingestive AG concentrations than participants without BE in both conditions. During the meal condition, postprandial decreases in AG concentrations were significantly smaller for the BE group than for the non-BE group. There were no significant differences in DAG by BE group. Leptin increased significantly less after meals for those with BE compared with those without BE. There were no differences in other hormones by BE group. Fasting and postmeal hunger ratings were significantly higher for those with BE than for those without BE.. In individuals with BE, lower fasting AG may be due to downregulation by habitual overeating, and a smaller postmeal decline in AG may contribute to overeating. Lower postmeal leptin concentrations may also contribute to overeating.

Topics: Adult; Appetite; Binge-Eating Disorder; Bulimia; Cholecystokinin; Eating; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Hyperphagia; Insulin; Leptin; Male; Meals; Middle Aged; Obesity; Peptide YY; Postprandial Period; Young Adult

Binge-eating disorder (BED), characterized by binge meals without purging afterward, is found in about 30% of obese individuals seeking treatment. The study objective was to ascertain abnormalities in hormones influencing appetite in BED, especially ghrelin, an appetite-stimulating peptide, which was expected to be elevated. Measurements were made of plasma insulin, leptin, glucagon, cholecystokinin, and ghrelin, as well as glucose following an overnight 12-h fast, prior to and after ingestion (from 0 to 5 min) of a nutritionally complete liquid meal (1254 kJ) at 0830 h, at -15, 0, 5, 15, 30, 60, 90, and 120 min. Appetite ratings including hunger and fullness were also obtained. An acetaminophen tracer was used to assess gastric emptying rate. Three groups of comparably obese women (BMI = 35.9 +/- 5.5; % body fat = 44.9 +/- 4.7) participated: 12 nonbinge eating normals (NB), 14 subthreshold BED, and 11 BED. The BED subjects, compared to NB subjects, had lower baseline ghrelin concentrations prior to the meal, a lower area under the curve (AUC), with lower levels at 5, 15, 30, 90, and 120 min, and a smaller decline in ghrelin postmeal (all P < 0.03). The other blood values did not differ among groups, and neither did gastric emptying rate nor ratings of fullness. The BED subjects were then randomly assigned to treatment with cognitive-behavior therapy and diet (n = 5) or to a wait-list control (n = 4). Baseline ghrelin (P = 0.01) and AUC increased (P = 0.02), across both conditions, in which most subjects (7 of 9) stopped binge eating. The lower fasting and postmeal plasma ghrelin levels in BED are consistent with lower ghrelin levels in obese compared to lean individuals and suggests downregulation by binge eating.

Topics: Adult; Appetite; Area Under Curve; Blood Glucose; Body Mass Index; Bulimia; Cholecystokinin; Cognitive Behavioral Therapy; Diet; Female; Ghrelin; Humans; Leptin; Obesity; Peptide Hormones; Postprandial Period; Premenopause; Reference Values

The core defining features of bulimia nervosa (BN) are repeated binge eating episodes and inappropriate compensatory (e.g., purging) behavior. Previous studies suggest an abnormal post-prandial response in the satiety-signaling peptide cholecystokinin (CCK) in persons with BN. It is unknown whether this altered response persists following remission or if it may be a potential target for the development of clinical treatment strategies. To examine the nature of this altered response, this study assessed whether CCK normalizes following remission from BN (RBN). This study prospectively evaluated the plasma CCK response and corresponding eating behavior-related ratings (e.g., satiety, fullness, hunger, urge to binge and vomit) in individuals with BN-purging subtype (n=10), RBN-purging subtype (n=14), and healthy controls (CON, n=13) at baseline, +15, +30, and +60 min following the ingestion of a standardized liquid test meal. Subject groups did not significantly differ in CCK response to the test meal. A significant relationship between CCK response and satiety ratings was observed in the RBN group (r=.59, p<.05 two-tailed). A new and unanticipated finding in the BN group was a significant relationship between CCK response and ratings of "urge to vomit" (r=.86, p<.01, two-tailed). Unlike previous investigations, CCK response did not differ in BN and CON groups. Thus the role of symptom severity remains an area of further investigation. Additionally, findings suggest that in this sample, CCK functioning following remission from BN-purging subtype is not different from controls. It remains unknown whether or not CCK functioning may be a protective or liability factor in the stabilization and recovery process. Replication studies utilizing a larger sample size are needed to further elucidate the role of CCK in recovery from BN and its potential target of related novel treatment strategies.

Topics: Adolescent; Adult; Bulimia; Bulimia Nervosa; Cholecystokinin; Eating; Female; Humans; Hunger; Middle Aged; Postprandial Period; Prospective Studies; Satiation

Binge eating disorder (BED), characterized by ingestion of very large meals without purging afterwards, is found in a subset of obese individuals. We showed previously that stomach capacity is greater in obese than in lean subjects, and in this study, we investigated capacity in obese individuals with BED. We also determined ad-libitum intake of a test meal until extremely full. Furthermore, we measured various appetitive hormones (insulin, leptin, glucagon, CCK, ghrelin) and glucose before a fixed meal and for 120 min afterwards. An acetaminophen tracer was used to assess gastric emptying rate. We compared three groups of overweight women: 11 BED, 13 BE (subthreshold BED), and 13 non-binge-eating normals. The BED individuals had the largest stomach capacity as assessed by either maximum volume tolerated (P=.05) or by gastric compliance to pressure (P=.02) using an intragastric balloon. Although test meal intake did not differ between groups, it correlated (P=.03) with gastric capacity. The BED group showed a tendency (P=.06) to have greater area under the curve (AUC) and had higher values at 5 and 60 min (P<.05) for insulin compared to normals. Moreover, the BED subjects had lower ghrelin baselines premeal, and lower AUC for ghrelin, which then declined less postmeal than for the normals (P<.05). None of the other blood values differed, including glucose, leptin glucagon, and CCK, as well as acetaminophen, reflecting gastric emptying. The lower ghrelin in BED, although contrary to what was expected, is consistent with lower ghrelin in obesity, and suggests down-regulation of ghrelin by overeating. The lack of differences in CCK is consistent with the lack of differences in gastric emptying rate, given that CCK is released when nutrients reach the intestine. The results show that BED subjects have a large gastric capacity as well as abnormalities in meal-related ghrelin and insulin patterns that may be factors in binge eating.

Topics: Adult; Appetite; Body Composition; Bulimia; Cholecystokinin; Eating; Female; Gastric Emptying; Ghrelin; Glucagon; Hormones; Humans; Leptin; Male; Peptide Hormones; Stomach; Surveys and Questionnaires

Increased amount of abdominal fat and obesity are common in polycystic ovary syndrome (PCOS). A higher prevalence of bulimia nervosa and greater cravings for sweets have also been reported in these patients. The present study aimed to compare meal-related appetite and secretion of the 'satiety peptide' cholecystokinin (CCK) and glucose regulatory hormones in PCOS women and controls. Sixteen pairs of women with PCOS and controls matched for age and body mass index participated in the study. After an overnight fast, blood samples were collected during ingestion of a standardized meal. We determined basal and postprandial blood levels of CCK, insulin, C-peptide, glucagon, cortisol, growth hormone and glucose. Self-ratings of appetite were assessed by a visual analog scale. PCOS women had a significantly lower meal-related CCK response (p < 0.05) with no association with satiety, as in the controls (r = 0.64). There was a tendency to higher ratings of craving for sweets in PCOS women (p = 0.07) but no correlation with insulin, as in the controls (r = 0.50). Within the PCOS group, ratings of craving for sweets were inversely related to testosterone (r = - 0.60) and the CCK response was positively correlated with levels of free testosterone (r = 0.50). We conclude that women with PCOS have reduced postprandial CCK secretion and deranged appetite regulation associated with increased levels of testosterone. Impaired CCK secretion may play a role in the greater frequency of binge eating and overweight in women with PCOS.

Topics: Adult; Appetite Regulation; Blood Glucose; Body Mass Index; Bulimia; C-Peptide; Cholecystokinin; Female; Food; Food Preferences; Glucagon; Human Growth Hormone; Humans; Hydrocortisone; Insulin; Polycystic Ovary Syndrome; Satiation; Sex Hormone-Binding Globulin; Testosterone

This study was designed to investigate the biological underpinnings of the observed deficit in satiety in patients with bulimia nervosa. Eight women with bulimia nervosa and 10 age- and weight-matched control subjects consumed three laboratory meals consisting of 200, 400, and 600 g of a radiolabeled liquid meal. For 1 h after each meal, blood samples were obtained at 10-min intervals for measurement of cholecystokinin concentration and gastric emptying was measured. Subjects also completed perceptual rating scales at 10-min intervals. Compared with control subjects, patients with bulimia nervosa showed a blunting of postprandial cholecystokinin release, particularly with larger meal sizes, as well as delayed gastric emptying. Increasing meal size was associated with increased desire to binge eat in patients but not in control subjects. These data lend support to a model in which increased gastric capacity, perhaps resulting from repeated binge eating, gives rise to delayed gastric emptying and blunted postprandial cholecystokinin release, leading to an impaired satiety response, which tends to perpetuate the illness.

Topics: Adolescent; Adult; Analysis of Variance; Bulimia; Cholecystokinin; Female; Gastric Emptying; Humans; Linear Models; Middle Aged; Postprandial Period; Satiation; Surveys and Questionnaires

Topics: Adolescent; Adult; Anorexia Nervosa; Bulimia; Cholecystokinin; Diet, Reducing; Dietary Fats; Female; Humans; Pancreatic Polypeptide; Postprandial Period; Reference Values

Topics: Bulimia; Cholecystokinin; Diet, Reducing; Energy Intake; Humans; Obesity; Satiation

The effect of a fat and protein rich test meal of 800 kcal on subjective satiety ratings and on plasma cholecystokinin (CCK) 8-S was studied in 18 acutely ill patients with anorexia nervosa, 11 former anorectic patients, who were weight recovered for at least 4 years, and in 25 healthy young women. Eleven normal weight patients with bulimia nervosa were studied in the same experiment. Satiety ratings were significantly elevated in acutely ill anorectic and bulimic patients. CCK 8-S values were significantly stimulated by the test meal in all groups except from the bulimic group. Anorectic patients and weight recovered anorectics had normal values before and after the test meal. Bulimic patients had significantly lower values. These data suggest that CCK 8-S is not involved in the regulation of short-term satiety in anorexia and bulimia nervosa.

Topics: Adult; Anorexia Nervosa; Body Weight; Bulimia; Cholecystokinin; Energy Intake; Female; Humans; Satiety Response

It has been shown that the gastrointestinal hormone cholecystokinin (CCK) induces satiety and reduces food intake in laboratory animals and humans. In the light of this evidence we studied CCK release in patients suffering from eating disorders. The secretion of CCK into the general circulation was measured in 10 anorectic, in 7 bulimic patients, and in 8 healthy controls before and after a high-caloric liquid testmeal. Baseline CCK values were similar in controls (0.6 +/- 0.2 pmol/l) and bulimics (0.6 +/- 0.1 pmol/l) and were significantly increased in the anorectic group (1.8 +/- 0.4 pmol/l) (p less than or equal to 0.005). After eating peak plasma levels increased to 6.1 +/- 0.9 pmol/l in the anorectic, to 3.8 +/- 0.5 pmol/l in the bulimic and to 2.7 +/- 0.6 pmol/l in the control group. All postprandial CCK values were significantly higher in the anorectic group. The secretion of CCK-8-S, an important peptide in the CCK family, was significantly elevated, too. This disturbed CCK secretion in patients suffering from anorexia nervosa, even if it is a secondary, diet-induced defect, may perpetuate this disorder.

Topics: Adolescent; Adult; Anorexia Nervosa; Bulimia; Cholecystokinin; Eating; Female; Gastrins; Humans; Male; Radioimmunoassay; Statistics as Topic

Bulimia nervosa is a prevalent disorder of unknown cause, characterized by recurrent episodes of uncontrollable eating. In the light of recent evidence that the gastrointestinal hormone cholecystokinin induces satiety and reduces food intake in laboratory animals and humans, we investigated the hypothesis that abnormalities in cholecystokinin secretion and satiety may occur in patients with bulimia and contribute to their disturbed eating patterns. Blood levels of cholecystokinin and subjective satiety were measured in 14 women with bulimia and 10 normal women before and after a mixed-liquid meal. The total integrated plasma cholecystokinin response to eating was significantly impaired in patients with bulimia (P less than 0.05) as was postprandial satiety. Fasting cholecystokinin levels were similar in both populations (approximately 0.8 pmol per liter). After eating, however, mean (+/- SEM) peak plasma cholecystokinin levels increased to 4.1 +/- 0.9 pmol per liter in normal controls but to only 2.1 +/- 0.2 pmol per liter in patients with bulimia nervosa (P less than 0.05). After an open trial of tricyclic antidepressants in a subgroup of five patients with bulimia, the postprandial cholecystokinin response to eating increased significantly, to 6.6 +/- 1.2 pmol per liter (P less than 0.05), and there was an increase in the satiety response. We conclude that patients with bulimia do not have normal satiety and have impaired secretion of cholecystokinin in response to a meal. Preliminary evidence suggests that both these abnormalities may be improved by treatment with tricyclic antidepressants.

Topics: Adolescent; Adult; Antidepressive Agents; Blood Glucose; Bulimia; Cholecystokinin; Eating; Female; Humans; Satiation

Topics: Bulimia; Cholecystokinin; Female; Humans; Male; Satiation