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Benzodiazepine receptor (BZR) agonists, used extensively for their anxiolytic effects, have been shown to increase food intake in many mammalian species. Little information, however, is available on the effects of BZR agonists on feeding behaviors of humans. Food intake was evaluated in a 60-minute free-feeding standardized test after the acute administration of the BZR agonist chlordiazepoxide (CDP, Librium; 5 mg or 20 mg) or placebo. Subjects were 12 individuals with the Prader-Willi syndrome (PWS), a disorder characterized by extreme hyperphagia and morbid obesity, and 11 controls with obesity. PWS subjects showed the characteristic hyperphagia associated with the appetite disorder, consuming more than six times as many sandwiches as controls with obesity. Results revealed no significant effect of either dose of CDP on the food intake of either group. Serum assays revealed that dose-dependent, clinically effective levels of CDP and active metabolites were achieved. These results suggest that acute administration of the BZR agonist CDP, at the therapeutic levels used, may not increase food intake in populations with obesity. However, the chronic effects of CDP on appetite in human populations still need to be explored.

We hypothesized that there is less suppression of whole-body protein breakdown with feeding in patients with cystic fibrosis (CF) who exhibit decreased insulin secretion after a single meal. Using [1-13C]leucine, we measured rates of nonoxidative leucine disappearance (whole-body protein synthesis) and protein breakdown in nine CF patients (6-11 y of age) and five healthy control subjects (8-10 y of age) during feeding and fasting. In the CF patients, synthesis and breakdown (x +/- SD) were 172 +/- 61 and 157 +/- 67 mumol.kg-1.h-1 during feeding and 140 +/- 24 and 178 +/- 26 mumol.kg-1.h-1 during fasting. The respective control values were 129 +/- 27 and 114 +/- 20 mumol.kg-1.h-1 during feeding and 136 +/- 13 and 173 +/- 18 mumol.kg-1.h-1 during fasting. Leucine balance was nearly identical in the two groups. By analysis of variance, there was a significant effect of feeding on protein breakdown but no difference between the groups. However, when each group was analyzed separately, feeding resulted in a 34% decrease in breakdown in the control subjects (P = 0.001) and a 23% increase in synthesis in the CF group (P = 0.058). Plasma insulin concentrations did not differ in the two groups. Thus, feeding may affect protein turnover differently in children with CF than in control children independently of plasma insulin concentration.

Prader-Willi syndrome is characterized by dramatic hyperphagia and morbid obesity, and is associated with a deficiency in basal and meal-stimulated serum pancreatic polypeptide (PP) levels. Intravenous infusions of pancreatic polypeptide (90 min, 50 pmol/kg/h) restored normal serum PP levels, and a regimen of morning and afternoon PP infusions was found to significantly reduce food intake in Prader-Willi subjects. Food intake was evaluated in a 60-min free-feeding test that shows high reliability and validity. Basal food intake during saline infusions was striking (approximately 60 chicken sandwich quarters), and this intake was reduced overall by approximately 12% during PP infusions. This reduction was apparent only for female subjects, and may have reflected enhanced satiation rather than an overall suppression of food intake. No differences were apparent across subjects, in either basal food intake or the PP-related decrease in food intake, in the presence or absence of the widely recognized chromosomal marker for this syndrome [deletion of 15(q11-q13)]. More specific gene defects as recently reported in these subjects, however, suggest that the Prader-Willi syndrome may represent an important model for the study of food intake regulation.