Plasma cholecystokinin levels in Prader-Willi syndrome and obese subjects

Abstract

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.

Appetite hormones and the transition to hyperphagia in children with Prader-Willi syndrome

“…28,39,41,45,48 In addition low fasting and postprandial insulin levels in PWS children and adults may be related more to preserved insulin sensitivity than reduced insulin secretion, as supported by reduced hypertriglyceridaemia and altered levels of related adipocytokines, such as increased plasma adiponectin in PWS. 23,24,29,30,34,38,45,48 Similar discrepancies have been seen for glucagon with fasting levels reported as low in one study of PWS children (410 years) and adults, 25 but normal fasting and post-prandial glucagon levels in another adult study. 35 …”

“…43 Similarly fasting plasma levels of the anorexigenic gut hormone GLP-1 that is cosecreted from intestinal L-cells with PYY appear normal in PWS children and adults, 10,34,38,48 and post-prandial GLP-1 levels are normal in PWS adults PWS. 10,38 Fasting and post-prandial plasma levels of CCK 11,23,25,41 and GIP, 21,38,45 other gut hormones involved in appetite regulation and glucose homeostasis, also appear normal in PWS children (over 7 --11 years) or adults. It therefore seems unlikely that deficiency of anorexigenic hormone PYY (or these other gut hormones) has a pathogenic role in hyperphagia in PWS.…”

Peptide YY, Cholecystokinin, Insulin and Ghrelin Response to Meal did not Change, but Mean Serum Levels of Insulin is Reduced in Children with Prader-Willi Syndrome

“…Batterham et al reported that the gut hormone fragment peptide YY 3-36 reduces appetite, food intake, and plasma ghrelin levels when infused into both normal weight and obese subjects (18, 27). Endogenous PYY levels were depressed in obese subjects, and the fasting PYY levels were found to correlate negatively with BMI (26).…”

Experimental Analyses of Gene‐brain‐behavior Relations: Some Notes on Their Application

“…In normal individuals, rises in free fatty acids are correlated with rises in CCK A (Guimbaud et al, 1997). Although baseline resting levels of plasma CCK A in people with Prader-Willi syndrome are not significantly different from control participants, they do not demonstrate the correlational rises in CCK A and free fatty acids after meals noted in control subjects (Butler, Carlson, Schmidt, Feurer, & Thompson, 2000). Thus, differences in response of peripheral CCK A to free fatty acid levels may result in an altered satiety response in individuals with Prader-Willi syndrome.…”