cholecystokinin and Anorexia-Nervosa

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

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

Topics: Animals; Anorexia Nervosa; Autonomic Nervous System; Body Weight; Brain; Cholecystokinin; Eating; Feeding Behavior; Gastric Emptying; Homeostasis; Humans; Hunger; Hypothalamus; Insulin; Intestinal Absorption; Liver; Obesity; Receptor, Insulin; Satiation; Thirst

Entero-insular axis plays an important role in generating satiety signal. Thus disturbances in this axis may influence the course of anorexia nervosa. The aim of the study was analysis of the function of the hormonal part of the entero-insular axis in girls with anorexia nervosa. Thirteen girls with anorexia nervosa and in 10 healthy girls were studied. Each girl was subjected to oral glucose tolerance test and standard meal test. Blood was collected before stimulation and within 15, 30, 60, and 120 min thereafter. The concentrations of all peptides were determined by radioimmunoassay commercial kits. Fasted and postprandial levels of these peptides as well as integrated outputs were measured. Fasting insulin concentration was significantly higher in the group of girls with anorexia nervosa than in the control group (p<0.03). What more in girls with anorexia the integrated output of insulin was significantly lower in oral glucose tolerance test than after the meal (p<0.001). Also the integrated output of glucagon in both tests was higher in the group of girls with anorexia than in the control group. The mean output of pancreatic polypeptide and cholecystokinin in anorexia group was significantly higher (p<0.001 in both cases) than that in the control group but only after the test meal. The integrated outputs of gastric inhibitory peptide in both tests were significantly higher in anorectic girls than those in the control group (oral glucose tolerance test, p<0.02; meal test, p<0.001), However, mean values of the integrated output of glucagon-like peptide 1 in both tests were significantly higher in the control group than in the girls with anorexia (p<0.001 in each case). Highly significant correlation was found between glucose concentration and the concentrations of insulin, cholecystokinin, and gastric inhibitory peptide in both tests and for the both groups. In the anorectic girls, significant correlation between insulin concentration and the concentration of gastric inhibitory peptide was found after both stimulation tests and between insulin and cholecystokinin after oral glucose only.. the disturbed secretion of the hormones of entero-insular axis after the meal in anorectic girls may have negative influence on the course of anorexia nervosa. This disease has no effect on the incretin function of cholecystokinin, gastric inhibitory peptide and glucagon-like peptide 1.

Topics: Adolescent; Anorexia Nervosa; Blood Glucose; Cholecystokinin; Eating; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Intestines; Pancreatic Polypeptide; Peptide Fragments; Protein Precursors; Signal Transduction

Anorexia nervosa (AN) is a syndrome of unknown cause characterized by voluntary starvation. Cholecystokinin has been implicated as a neuroendocrine regulatory factor in control of satiety. Relatively little information is known about gastrointestinal hormone responses to feeding in subjects with anorexia nervosa. In the present studies, we examine fasting and postprandial levels of cholecystokinin (CCK), vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in anorexia nervosa subjects and in control individuals. Results of these studies indicate that plasma CCK response to a liquid meal (Ensure Plus) in untreated AN subjects was distinctly different from that observed in healthy controls, both in terms of temporal pattern of peptide released and the amount of CCK secreted into the circulation. Peak levels of CCK release occurred at 30 min following meal ingestion in AN patients and at 60 min in control subjects. Integrated CCK release in untreated AN patients was approximately twice that measured in control individuals. Renutrition therapy was associated with reversion of the pattern of CCK release to that observed in control subjects. Plasma VIP levels were unchanged following meal ingestion in both control and anorexic subjects. In contrast, PHM levels in AN subjects were significantly greater than that observed in control individuals. The pattern of PHM release following liquid meal ingestion was similar to that observed with plasma CCK; namely, peak release of peptide was observed at 30 min which was significantly greater than corresponding control values (P less than 0.05). In conclusion, these results demonstrate distinctive differences in plasma CCK and PHM levels in response to feeding in AN subjects when compared to control individuals. These findings suggest that the earlier and greater rise in plasma CCK levels in AN subjects following meal ingestion may contribute to the abnormal sensation of satiety in this condition.

Topics: Anorexia Nervosa; Cholecystokinin; Diet Therapy; Eating; Female; Food, Formulated; Gastrointestinal Hormones; Humans; Peptide PHI; Plasma; Vasoactive Intestinal Peptide

(1) The objective of this study is to analyze differences in smell-taste capacity between females in extreme weight/eating conditions (EWC) and (2) to explore the interaction between smell/taste capacity, gastric hormones, eating behavior and body mass index (BMI). The sample comprised 239 females in EWC [64 Anorexia nervosa (AN) and 80 age-matched healthy-weight controls, and 59 obese and 36 age-matched healthy-weight controls]. Smell and taste assessments were performed through "Sniffin' Sticks" and "Taste Strips," respectively. The assessment measures included the eating disorders inventory-2, the symptom check list 90-revised, and The Dutch Eating Behavior Questionnaire, as well as peptides from the gastrointestinal tract [Ghrelin, peptide YY, cholecystokinin]. Smell capacity was differentially associated across EWC groups. Smell was clearly impaired in obese participants and increased in AN (hyposmia in Obesity was 54.3 and 6.4 % in AN), but taste capacity did not vary across EWC. Ghrelin levels were significantly decreased in obese subjects and were related to smell impairment. EWC individuals showed a distinct smell profile and circulating ghrelin levels compared to controls. Smell capacity and ghrelin may act as moderators of emotional eating and BMI.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Weight; Cholecystokinin; Feeding Behavior; Female; Ghrelin; Humans; Middle Aged; Obesity; Olfaction Disorders; Peptide YY; Smell; Taste; Taste Disorders; Young Adult

Despite a number of studies in the past decades, the role of Cholecystokinin (CCK) in anorexia nervosa (AN) has remained uncertain. In this study a highly specific assay for the biologically active part of CCK was used in patients with bulimic as well as with the restricting type of AN who were followed over the course of weight gain.. Ten patients with restricting and 13 with bulimic AN were investigated upon admission (T0), after a weight gain of at least 2 kg on two consecutive weighting dates (T1), and during the last week before discharge (T2) from inpatient treatment in a specialized clinic. Blood samples were drawn under fasting conditions and 20 and 60 minutes following a standard meal (250 kcal). Data were compared to those of eight controls matched for sex and age. Gastrointestinal complaints of patients were measured by a questionnaire at each of the follow-up time points.. At admission, AN patients exhibited CCK-levels similar to controls both prior to and after a test meal. Pre and post-meal CCK levels increased significantly after an initial weight gain but decreased again with further weight improvement. CCK release was somewhat lower in bulimic than in restricting type AN but both subgroups showed a similar profile. There was no significant association of CCK release to either initial weight or BMI, or their changes, but CCK levels at admission predicted gastrointestinal symptom improvement during therapy.. Normal CCK profiles in AN at admission indicates hormonal responses adapted to low food intake while change of eating habits and weight gain results in initially increased CCK release (counteracting the attempts to alter eating behavior) that returns towards normal levels with continuous therapy.

Topics: Adult; Anorexia Nervosa; Cholecystokinin; Eating; Feeding Behavior; Female; Follow-Up Studies; Humans; Hunger; Male; Middle Aged; Surveys and Questionnaires; Weight Gain

Topics: 3' Untranslated Regions; Anorexia Nervosa; Cholecystokinin; Genetic Carrier Screening; Humans; Netherlands; Polymorphism, Genetic

Cholecystokinin (CCK), glucose dependent insulinotropic peptide (GIP), and glucagon-like peptide 1 (GLP-1) regulate satiety as enterogastrons and incretins. They also directly affect the satiety centers. Therefore, these peptides may participate in the pathogenesis of eating disorders. CCK, GIP, and GLP-1 secretion were studied in 13 adolescent girls suffering from simple obesity, 13 girls with anorexia nervosa, and 10 healthy girls. Each girl was subjected to an oral glucose tolerance test (OGTT) and standard meal test. Blood was collected before stimulation and at 15, 30, 60, and 120 min. The concentrations of all peptides were determined by RIA commercial kits. Fasting and postprandial levels of these peptides as well as integrated outputs were measured. High postprandial levels of CCK observed in the girls with anorexia may aggravate the course of this disease by intensifying nausea and vomiting. Low postprandial level of GLP-1 in girls with simple obesity may be responsible for excessive ingestion of food and weaker inhibition of gastric emptying, which also leads to obesity.

Topics: Adolescent; Anorexia Nervosa; Child; Cholecystokinin; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Male; Obesity; Peptide Fragments; Protein Precursors; Radioimmunoassay

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

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

There is considerable evidence that the gastrointestinal hormone cholecystokinin (CCK) induces satiety and reduces food intake in both animals and humans. Impaired CCK secretion was recently reported in patients with bulimia nervosa (BN) in whom plasma CCK responses to a standardized mixed-liquid meal were significantly lower than in controls. The present study was undertaken to determine whether CCK levels were abnormal in another relatively common eating disorder, anorexia nervosa (AN), before and after therapy and to investigate the relationship to the abnormal eating behavior. Plasma CCK, serum glucose, and immunoreactive insulin (IRI) responses to a 50-g oral glucose load were measured in 13 women with AN and in nine normal sex- and age-matched controls. The AN patients were all hospitalized during treatment; following partial restoration of body weight, the tests were repeated. Initial body weights were 70.8% +/- 1.8% (mean +/- SEM) of ideal body weight (IBW), and following partial restoration were 84.3% +/- 1.4%. Body weights in normal controls were 96.3% +/- 2.1% of IBW. Initial basal CCK concentrations in the AN patients before nutritional and cognitive behavioral therapy were significantly greater than those in controls (P < .01). After partial restoration of body weight, basal CCK concentration in AN patients approached that of control subjects. When AN patients were given a glucose load before therapy, the change in CCK response was diminished when compared with that of controls. However, CCK responses to the glucose load in AN patients following therapy were similar to those of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Anorexia Nervosa; Blood Glucose; Body Weight; Cholecystokinin; Female; Glucose Tolerance Test; Humans; Insulin; Osmolar Concentration; Reference Values

Six patients with anorexia nervosa, the same patients after weight normalization, and six healthy control subjects had similar fasting and postprandial plasma cholecystokinin concentrations. These data do not support the hypothesis that low levels of hunger and food intake in anorexic patients reflect hypersecretion of this endogenous hormone, which is thought to inhibit hunger, promote satiety, and reduce feeding.

Topics: Adult; Anorexia Nervosa; Appetite Regulation; Blood Glucose; Body Weight; Cholecystokinin; Eating; Female; Humans; Hunger; Satiation

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

Topics: Animals; Anorexia Nervosa; Antipsychotic Agents; Apomorphine; Brain; Cholecystokinin; Glutamine; Humans; Mesencephalon; Neurons; Proglumide; Receptors, Dopamine; Schizophrenia

Immunoreactive somatostatin, bombesin, and cholecystokinin were measured in cerebrospinal fluid of normal subjects and patients with anorexia nervosa, depression, mania, and schizophrenia. Somatostatin-like immunoreactivity was decreased in anorexic and depressed patients. Bombesin-like immunoreactivity tended to be decreased in schizophrenics. Cholecystokinin-like immunoreactivity did not differ between groups. These data suggest a possible function for neuropeptides in regulation of human behavior.

Topics: Adult; Anorexia Nervosa; Bipolar Disorder; Bombesin; Cholecystokinin; Depressive Disorder; Female; Humans; Male; Mental Disorders; Peptides; Schizophrenia; Somatostatin