Research Notes: Cholecystokinin

Am J Med Genet. 2000 Nov 6.
Plasma cholecystokinin levels in Prader-Willi syndrome and obese subjects.
Butler MG, Carlson MG, Schmidt DE, Feurer ID, Thompson T.
Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA.

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.

Pancreas. 1989.
Protein meal-stimulated pancreatic polypeptide secretion in Prader-Willi syndrome of adults.
Tomita T, Greeley G Jr, Watt L, Doull V, Chance R.
Department of Pathology, University of Kansas Medical Center, Kansas City.

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.