Prader-Willi syndrome: advances in genetics, pathophysiology and treatment

Goldstone, Anthony P.

doi:10.1016/j.tem.2003.11.003

Cited by 353 publications

(287 citation statements)

References 88 publications

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“…Interestingly, the two groups were also matched for central adiposity and insulin resistance without specific selection of control subjects. Although our PWS cohort might seem unusual, as a lower visceral fat mass and preserved insulin sensitivity has been reported previously (Brambilla et al, 1997, Goldstone et al, 2001, Goldstone et al, 2004, Goldstone et al, 2005, Talebizadeh and Butler, 2005, Kennedy et al, 2006, Theodoro et al, 2006, Haqq et al, 2010and Sode-Carlsen et al, 2010, other investigators recently reported similar observations to ours, i.e. obese children and adults with PWS having the same amount of visceral fat mass, the same degree of insulin resistance and a similar prevalence of metabolic syndrome compared to carefully weight-matched obese subjects Butler, 2005 andBrambilla et al, 2010).…”

Section: Discussionsupporting

confidence: 86%

“…A 2004 study (Goldstone et al, 2004) assessed fasting plasma GLP-1[total] in 12 female and 16 male adults with PWS, and found different between groups (Fig. 2E).…”

Section: Discussionmentioning

confidence: 98%

“…A 2004 study (Goldstone et al, 2004) assessed fasting plasma GLP-1[total] in 12 female and 16 male adults with PWS, and found no difference in levels compared to obese and lean controls. However, as the authors noted, there may be postprandial changes in secretion of GLP-1 in PWS not measured in their study.…”

Section: Discussionmentioning

confidence: 99%

“…Prader-Willi syndrome (PWS), with an incidence of approximately 1 in 15,000, is a leading genetic cause of obesity, caused by a loss of expression of paternally imprinted genes on chromosome 15q11-q13 (Goldstone, 2004). After initial severe hypotonia and failure to thrive in infancy, children with PWS develop hyperphagia with weight gain, with onset at 2-6 years (Butler, 1990).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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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.

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Section: Discussionsupporting

confidence: 86%

“…A 2004 study (Goldstone et al, 2004) assessed fasting plasma GLP-1[total] in 12 female and 16 male adults with PWS, and found different between groups (Fig. 2E).…”

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2011

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“…There is some evidence to suggest a hypothalamic basis, 7,8 which was recently supported by a functional neuroimaging study in three individuals with PWS. 9 Shapira et al 9 showed a significant delay in the negative response of the hypothalamus to glucose ingestion in those with PWS, in comparison to obese 10 and normal-weight 11 groups.…”

Section: Introductionmentioning

confidence: 85%

Neural representations of hunger and satiety in Prader–Willi syndrome

et al. 2005

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Objective: To investigate the neural basis of the abnormal eating behaviour in Prader-Willi syndrome (PWS), using brain imaging. We predicted that the satiety response in those with PWS would be delayed and insensitive to food intake. Design and participants: The design of this study was based on a previous investigation of the neural activation associated with conditions of fasting and food intake in a nonobese, non-PWS group. The findings were used to generate specific hypotheses regarding brain regions of interest for the current study, in which 13 adults with PWS took part (mean7s.d. age ¼ 2976; BMI ¼ 31.575.1; IQ ¼ 7178, six were female). Measurements: Regional cerebral blood flow was measured using positron emission tomography in three sessions: one following an overnight fast and two following disguised energy controlled meals of similar volume and appearance -one of 1674 kJ (400 kcal) and another of 5021 kJ (1200 kcal). Subjective ratings of hunger, fullness and desire to eat, and blood plasma levels of glucose, insulin, leptin, ghrelin and PYY were measured before and after each imaging session. Results: The neural representation of hunger, after an overnight fast, was similar to that found in nonobese individuals in the control study. In contrast, after food intake, the patterns of neural activation previously associated with satiety were not found, even after the higher-energy load. Lateral and medial orbitofrontal cortical activation was associated with consumption of the 400-and 1200-kcal meals, respectively. The medial orbitofrontal activation, however, was only found in those who had shown a large percentage change in fullness ratings following the higher-energy meal. Conclusion: We conclude that there is a dysfunction in the satiety system in those with PWS. These findings suggest that brain regions associated with satiety are insensitive even to high-energy food intake in those with the syndrome. This may be the neural basis of the hyperphagia seen in PWS.

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Weight Regulation and Monogenic Obesity

Farooqi¹

2005

Clinical Pediatric Endocrinology

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Prader-Willi syndrome: advances in genetics, pathophysiology and treatment

Cited by 353 publications

References 88 publications

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

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

Neural representations of hunger and satiety in Prader–Willi syndrome

Weight Regulation and Monogenic Obesity

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