In adults with Prader–Willi syndrome, elevated ghrelin levels are more consistent with hyperphagia than high PYY and GLP-1 levels

Abstract

ObjectivePrader-Willi syndrome (PWS) is a leading genetic cause of obesity, characterized by hyperphagia, endocrine and developmental disorders. It is suggested that the intense hyperphagia could stem, in part, from impaired gut hormone signaling. Previous studies produced conflicting results, being confounded by differences in body composition between PWS and control subjects. Design Fasting and postprandial gut hormone responses were investigated in a cross-sectional cohort study including 10 adult PWS, 12 obese subjects matched for percentage body fat and central abdominal fat, and 10 healthy normal weight subjects. Methods PYY [total], PYY , GLP-1[active] and ghrelin [total] were measured by ELISA or radioimmunoassay. Body composition was assessed by dual energy X-ray absorptiometry. Visual analog scales were used to assess hunger and satiety. Results In contrast to lean subjects (p < 0.05), PWS and obese subjects were similarly insulin resistant and had similar insulin levels. Ghrelin[total] levels were significantly higher in PWS compared to obese subjects before and during the meal (p < 0.05). PYY meal responses were higher in PWS than in lean subjects (p = 0.01), but not significantly different to obese (p = 0.08), with an additional non-significant trend in PYY[total] levels. There were no significant differences in self-reported satiety between groups, however PWS subjects reported more hunger throughout (p = 0.003), and exhibited a markedly reduced mealinduced suppression of hunger (p = 0.01) compared to lean or obese subjects. Conclusions Compared to adiposity-matched control subjects, hyperphagia in PWS is not related to a lower postprandial GLP-1 or PYY response. Elevated ghrelin levels in PWS are consistent with increased hunger and are unrelated to insulin levels.

The glucagon-like peptide-1 analog liraglutide suppresses ghrelin and controls diabetes in a patient with Prader-Willi syndrome

“…The finding indicates that GLP-1 suppression of ghrelin is impaired and physiological postprandial excursion of GLP-1 may not be followed by appropriate lowering of ghrelin in this syndrome. Hyperphagia in PWS patients is thought not to be related to a lower postprandial GLP-1 response, and elevated ghrelin levels in PWS are consistent with increased hunger and they are unrelated to insulin levels [3].…”

“…However, as GLP-1 is secreted in response to nutrient intake, differences may exist postprandially. Regrettably, we did not evaluate the postprandial response of active GLP-1, although it was recently reported that the postprandial response of active GLP-1 was no different between PWS and control subjects [3].…”

“…However, it was recently suggested that the intense hyperphagia in PWS could stem, at least in part, from impaired gut hormone signaling [3].…”

Prader–Willi syndrome: genotype, cause, phenotype and management

“…Research into the role of hormones and proteins in PWS aims to ascertain the precise underlying dysfunction to determine potential treatments; however, no clear understanding exists and reports are often contradictory (Purtell et al, 2011).…”

“…Recent research topics include: Insulin sensitivity -this is higher in people with PWS; however, the role of insulin in PWS remains obscure with a suggestion of a differing role in No longer has an insatiable appetite and is able to feel full Only observed in adulthood From: Miller et al (2011) clinical PWS (Haqq et al, 2011), although no definite evidence is available (Purtell et al, 2011) Ghrelin -this is an orexogenic hormone produced in the stomach and pancreas that increases appetite; higher levels have been reported in people with PWS (Miller et al, 2011;Purtell et al, 2011; PWSA(UK), 2012) and Yi et al (2011) reported altered levels, but McAllister and colleagues (2011) suggest that the role in PWS has yet to be fully established Peptide YY (PYY) -this is a pancreatic polypeptide with anorexigenic actions (appetite suppressant); low levels of this hormone are reported in people with PWS (PWSA(UK), 2012), although its role in PWS has yet to be established (Purtell et al, 2011) Glycogen-like peptide-1 (GLP-1) -this has several functions, including increasing insulin secretion and satiety; however, its role in PWS has yet to be established (Purtell et al, 2011) Fat distribution in people with PWSdifferences in fat distribution can influence hormone levels; however, in PWS there is currently no clear understanding (Haqq et al, 2011;Purtell et al, 2011) Genetics -no direct link has been established to genes located at 15q11.2-13; it is therefore suggested that the consequence of genetics on the hypothalamic feeding pathway and the role of the prenatal environment remain key research areas (McAllister et al, 2011). There is no effective medication available for hyperphagia and obesity (Cassidy and Driscoll, 2009;Butler, 2011;McAllister et al, 2011;Purtell et al, 2011;PWSA(UK), 2012).…”