Plasma cholecystokinin levels in Prader-Willi syndrome and obese subjects

The cardinal feature of individuals with Prader-Willi syndrome (PWS) is sev ere hyperphagia-mediated obesity resulting from a faulty satiety mechanism. PWS is the most common genetic cause of marked obesity. Cholecystokinin (C CK) is a 33-amino-acid peptide found in high levels in the gut and brain in volved in mediating the satiety response to meals. Free fatty acids (FFA) a re responsible for the stimulation of CCK release after a fatty meal, and C CK and plasma FFA levels rise in tandem in normal individuals. Fasting plas ma 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 mum/ mL) or CCK levels (21.0 versus 19.1 pg/mL) were signifi cantly different in PWS or control subjects, respectively. However, there w as a significant correlation between fasting plasma FFA and CCK levels in o bese 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 coef ficients constitutes a large effect. There were no significant effects obse rved for genetic subtypes (15q11-q13 deletion or maternal disomy 15), body mass index, percentage of fat, plasma levels of insulin, C-peptide, glucago n or leptin, age, or gender on CCK levels in our PWS subjects. These result s suggest that differences in the peripheral CCK response to FFA levels may be a factor contributing to the altered satiety response in PWS subjects. (C) 2000 Wiley-Liss, Inc.