The cause of the unique elevation in fasting plasma levels of the orexigenic gastric
hormone ghrelin in many patients with
Prader-Willi syndrome (PWS) is unclear. We measured fasting and postprandial plasma
ghrelin in nonobese (n = 16 fasting and n = 8 postprandial) and obese non-PWS adults (n = 16 and 9), adults with genetically confirmed PWS (n = 26 and 10), and patients with hypothalamic
obesity from
craniopharyngioma tumors (n = 9 and 6). We show that 1) plasma
ghrelin levels decline normally after food consumption in PWS, but there is still fasting and postprandial hyperghrelinemia relative to the patient's
obesity (2.0-fold higher fasting
ghrelin, 1.8-fold higher postprandial
ghrelin, adjusting for percentage of body fat); 2) the fasting and postprandial hyperghrelinemia in PWS appears to be at least partially, but possibly not solely, explained by the concurrent relative hypoinsulinemia and preserved
insulin sensitivity for the patient's
obesity (residual 1.3- to 1.6-fold higher fasting
ghrelin, 1.2- to 1.5-fold higher postprandial
ghrelin in PWS, adjusting for
insulin levels or homeostasis model assessment of
insulin resistance); 3) hyperghrelinemia and hypoinsulinemia are not found in
craniopharyngioma patients with hypothalamic
obesity, and indeed, these patients have relative
hyperinsulinemia for their
obesity; and 4) there is no deficiency of the anorexigenic
intestinal hormone peptide YY(3-36) in PWS contributing to their hyperghrelinemia.