cholecystokinin and Prader-Willi-Syndrome

Prader-Willi syndrome (PWS) is a contiguous gene syndrome characterized by uncontrollable eating or hyperphagia. Several studies have confirmed that plasma ghrelin levels are markedly elevated in PWS adults and children. The study of anorexigenic hormones is of interest because of their regulation of appetite by negative signals. To study the pattern and response of the anorexigenic hormones such as cholecystokinin (CCK) and peptide YY (PYY) to a meal in PWS, we measured the plasma CCK, PYY, ghrelin and serum insulin levels in PWS patients (n=4) and in controls (n=4) hourly for a day, and analyzed hormone levels and hormonal responses to meals. Repeated measures of ANOVA of hormone levels demonstrated that only insulin levels decreased (p=0.013) and CCK (p=0.005) and ghrelin (p=0.0007) increased in PWS over 24 hr. However, no significant group x time interactions (ghrelin: p=0.89, CCK: p=0.93, PYY: p=0.68 and insulin: p=0.85) were observed; in addition, there were no differences in an assessment of a three-hour area under the curve after breakfast. These results suggest that the response pattern of hormones to meals in PWS patients parallels that of normal controls. In addition, the decrease of insulin levels over 24 hr, in spite of obesity and elevated ghrelin levels, suggests that the baseline insulin level, not the insulin response to meals, may be abnormal in patients with PWS.

Topics: Adolescent; Area Under Curve; Biopsy; Body Mass Index; Body Weight; Child; Cholecystokinin; Ghrelin; Humans; Insulin; Male; Obesity; Peptide Hormones; Peptide YY; Prader-Willi Syndrome; Time Factors

The cardinal feature of individuals with Prader-Willi syndrome (PWS) is severe hyperphagia-mediated obesity resulting from a faulty satiety mechanism. PWS is the most common genetic cause of marked obesity. Cholecystokinin (CCK) is a 33-amino-acid peptide found in high levels in the gut and brain involved in mediating the satiety response to meals. Free fatty acids (FFA) are responsible for the stimulation of CCK release after a fatty meal, and CCK and plasma FFA levels rise in tandem in normal individuals. Fasting plasma CCK levels were measured by radio-immunoassay in 33 PWS subjects with a mean age of 22.2 years +/- 8.1 years and 24 obese control subjects without a known cause of their obesity with a mean age of 28.7 years +/- 12.9 years. Consistent with previous findings, neither fasting plasma FFA levels (617.5 versus 486.8 microm/mL) or CCK levels (21.0 versus 19.1 pg/mL) were significantly different in PWS or control subjects, respectively. However, there was a significant correlation between fasting plasma FFA and CCK levels in obese subjects (r = 0. 64, P < 0.01), this correlation was completely lacking in PWS subjects (r = -0.06, P = 0.79). This difference in correlation coefficients constitutes a large effect. There were no significant effects observed for genetic subtypes (15q11-q13 deletion or maternal disomy 15), body mass index, percentage of fat, plasma levels of insulin, C-peptide, glucagon or leptin, age, or gender on CCK levels in our PWS subjects. These results suggest that differences in the peripheral CCK response to FFA levels may be a factor contributing to the altered satiety response in PWS subjects.

Topics: Adolescent; Adult; Cholecystokinin; Fatty Acids, Nonesterified; Female; Humans; Male; Obesity; Prader-Willi Syndrome

The behavioural, cognitive and metabolic response to food intake was studied in 13 adults with the Prader-Willi syndrome (PWS) and compared to ten age-matched controls. Rates of eating were observed during one hour's access to food and feelings of hunger were assessed using a visual analogue scale. Blood was taken for estimation of glucose, insulin, cholecystokinin (CCK), prolactin, growth hormone (GH) and cortisol every 20 min for a total period of 100 min. Ten (76%) of the subjects with PWS ate steadily for the whole hour that food was available and on average consumed three times more calories than the control group. The median ratings for feelings of hunger in the PWS group changed in the expected direction but these changes were delayed compared to the control group and only reached the same level as the controls after the PWS subjects had eaten a significantly greater amount of food. In the PWS group, in contrast to the control group, feelings of hunger started to re-emerge shortly after food was removed. There were marked differences between individuals with PWS in the extent of the changes in serum prolactin levels. Increases in plasma glucose levels were inversely correlated with changes in hunger ratings in the PWS group, but not the control group. There was a significantly greater increase in serum CCK levels during the meal in the PWS group than in the control group indicating that in PWS failure of peripheral release of CCK in response to food intake was not the explanation for the impaired satiety response.

Topics: Adolescent; Adult; Appetite; Blood Glucose; Cholecystokinin; Feeding Behavior; Hormones; Humans; Hunger; Prader-Willi Syndrome; Satiation

Children with Prader-Willi syndrome (PWS) are characterized by obesity, hyperphagia, hypogonadism, and mental retardation with underlying hypothalamic dysfunction and are known to have blunted or absent pancreatic polypeptide (PP) secretion in response to protein meals. In this communication, adults (26 +/- 3 years of age) with PWS were compared with age-matched normal obese and normal weight controls in regards to plasma glucose, insulin, PP, cholecystokinin (CCK), cholesterol, and triglyceride after a high protein meal. Compared with normal weight controls, adults with PWS showed a smaller and delayed rise in plasma insulin, and relatively smaller and delayed PP elevation whereas obese controls revealed hyperglycemia, markedly higher insulin, and moderately higher PP, cholesterol, and triglyceride levels than those with PWS. There was a small increment of CCK levels after a protein meal in all groups of adults. After a protein meal, the molar ratio of PP to CCK doubled in normal weight and PWS groups, and this ratio tripled in the normal obese group, suggesting no reduced PP secretion in PWS in response to CCK stimulation. PP hyposecretion in PWS thus appears to be a part of multiple endocrinopathy associated with hypothalamic dysfunction.

Topics: Adult; Cholecystokinin; Cholesterol; Dietary Proteins; Female; Humans; Insulin; Male; Obesity; Pancreatic Polypeptide; Prader-Willi Syndrome; Triglycerides