Serum Ghrelin Levels Are Inversely Correlated with Body Mass Index, Age, and Insulin Concentrations in Normal Children and Are Markedly Increased in Prader-Willi Syndrome

Haqq, Andrea M.; Farooqi, I. Sadaf; O’Rahilly, Stephen; Stadler, Diane D.; Rosenfeld, Ron G.; Pratt, Katherine L.; LaFranchi, Stephen; Purnell, Jonathan Q.

doi:10.1210/jc.2002-021052

Cited by 352 publications

(274 citation statements)

References 27 publications

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“…The present study confirms previous reports (DelParigi et al, 2002, Haqq et al, 2003, Goldstone et al, 2004and Tauber et al, 2004) that fasting and postprandial ghrelin levels are significantly higher in PWS subjects compared to obese and lean subjects. However, in contrast to previous reports , Goldstone et al, 2004, Goldstone et al, 2005and McLaughlin et al, 2004, our data suggest that the observed increase in ghrelin in PWS is not due to altered fat distribution or hypoinsulinemia because PWS and obese subjects were matched for total and central adiposity and showed similar insulin secretion and insulin resistance.…”

Section: Discussionsupporting

confidence: 93%

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: 93%

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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“…In contrast to the imaging results, the blood plasma levels of glucose, insulin, ghrelin and PYY were found in accordance with the predictions: levels of all of the above were significantly different between the fasting and high-energy meal conditions. While ghrelin levels were elevated in comparison to controls in previously published literature, 35,[41][42][43] recent work has shown that even when ghrelin levels are reduced to a normal level, using somatostatin or a somatostatin agonist, there is no effect on appetite or food intake in individuals with PWS. 44,45 This suggests that the dysfunction in PWS is central in origin, rather than as a result of abnormalities in the periphery, at least in terms of the measures in this study.…”

Section: Discussionmentioning

confidence: 70%

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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“…A reduction in plasma ghrelin in the obese A y /a mouse is consistent with the low plasma ghrelin found in obese humans. [37][38][39] The reduction in Arc NPY mRNA expression in obese A y /a mice may contribute to their increased linear growth. Our observation is in contrast to a previous study of obese A y /a mice of a comparable age and body weight that used similar techniques.…”

Section: Discussionmentioning

confidence: 99%

Abnormalities of the somatotrophic axis in the obese agouti mouse

et al. 2005

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Objective: Abnormalities of the melanocortin system produce obesity and increased linear growth. While the obesity phenotype is well characterised, the mechanism responsible for increased linear growth is unclear. The somatotrophic axis was studied in the obese agouti (A y /a) mouse as a model of a perturbed melanocortin system. Design: Adult obese A y /a mice were compared to age-and sex-matched wild-type (WT) controls. Weight and body length (nose-anus) were recorded. Plasma growth hormone (GH), insulin-like growth factor-I (IGFI), insulin and leptin were measured using radioimmunoassay. Since ghrelin is a potent GH secretagogue, plasma ghrelin, stomach ghrelin peptide and stomach ghrelin mRNA expression were studied. Hypothalamic periventricular (PeVN) somatostatin neurones and arcuate (Arc) neuropeptide Y (NPY) neurones inhibit the growth axis, whereas Arc growth hormone-releasing hormone (GHRH) neurones are stimulatory. Therefore, specific hypothalamic expression of somatostatin, NPY and GHRH was measured using quantitative in situ hybridisation. Results: Obese A y /a mice were significantly heavier and longer than WT controls. Plasma IGFI concentrations were 30% greater in obese A y /a mice. Obese A y /a mice were hyperinsulinaemic and hyperleptinaemic, yet plasma ghrelin, and stomach ghrelin peptide and mRNA were significantly reduced. In obese A y /a mice, PeVN somatostatin and Arc NPY mRNA expression were reduced by 50% compared to WT controls, whereas Arc GHRH mRNA expression was unchanged. Conclusion: Increased body length in adult obese A y /a mice may result from reduced Arc NPY and PeVN somatostatin mRNA expression, which in turn, may increase plasma IGFI concentrations and upregulate the somatotrophic axis.

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Serum Ghrelin Levels Are Inversely Correlated with Body Mass Index, Age, and Insulin Concentrations in Normal Children and Are Markedly Increased in Prader-Willi Syndrome

Cited by 352 publications

References 27 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

Abnormalities of the somatotrophic axis in the obese agouti mouse

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