Hyperghrelinemia Precedes Obesity in Prader-Willi Syndrome

Feigerlová, Eva; Diene, Gwénaëlle; Conte-Auriol, F.; Molinas, Catherine; Gennero, Isabelle; Salles, Jean‐Pierre; Arnaud, Catherine; Tauber, Maïthé

doi:10.1210/jc.2007-2138

Cited by 125 publications

(106 citation statements)

References 34 publications

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“…Some studies have shown elevated ghrelin levels in PWS infants and children and thus it appears that hyperghrelinemia may precede hyperphagia in PWS, though this has not been universally seen in all studies (Erdie-Lalena et al, 2006;Feigerlova et al, 2008;Haqq et al, 2008). Neonatal transgenic deletion PWS mice die from severe neonatal hypoglycemia due to depletion of liver glycogen stores, and ghrelin levels increase reciprocally with the falling glucose levels (Stefan et al, 2005) Although it has been hypothesised that hyperphagia in PWS may be partly explained by rapid gastric emptying due to increased gastric motility caused by elevated ghrelin levels, in fact patients with PWS have delayed gastric emptying (Choe et al,…”

mentioning

confidence: 99%

Ghrelin in obesity and endocrine diseases

Scerif

Goldstone

Korbonits

2011

Molecular and Cellular Endocrinology

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mentioning

confidence: 99%

Ghrelin in obesity and endocrine diseases

Scerif

Goldstone

Korbonits

2011

Molecular and Cellular Endocrinology

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“…However, this conclusion is contradicted by the largest study that found elevated fasting plasma ghrelin levels in PWS children under 3 years. 47 It is possible that these discrepancies are related to the smaller size of the negative studies, including our own. 39,42,46 Furthermore, hyperghrelinaemia in older children and PWS adults may be partially, though not solely, explained by preserved insulin sensitivity and relative hypoinsulinaemia, as ghrelin levels are negatively correlated with insulin.…”

Section: Ghrelinmentioning

confidence: 86%

Appetite hormones and the transition to hyperphagia in children with Prader-Willi syndrome

et al. 2012

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OBJECTIVE: Prader --Willi syndrome (PWS) is a genetic neurodevelopmental disorder with several nutritional phases during childhood proceeding from poor feeding, through normal eating without and with obesity, to hyperphagia and life-threatening obesity, with variable ages of onset. We investigated whether differences in appetite hormones may explain the development of abnormal eating behaviour in young children with PWS. SUBJECTS: In this cross-sectional study, children with PWS (n ¼ 42) and controls (n ¼ 9) aged 7 months --5 years were recruited. Mothers were interviewed regarding eating behaviour, and body mass index (BMI) was calculated. Fasting plasma samples were assayed for insulin, leptin, glucose, peptide YY (PYY), ghrelin and pancreatic polypeptide (PP). RESULTS: There was no significant relationship between eating behaviour in PWS subjects and the levels of any hormones or insulin resistance, independent of age. Fasting plasma leptin levels were significantly higher (mean±s.d.: 22.6±12.5 vs 1.97 ± 0.79 ng ml À1 , P ¼ 0.005), and PP levels were significantly lower (22.6 ± 12.5 vs 69.8 ± 43.8 pmol l À1 , Po0.001) in the PWS group compared with the controls, and this was independent of age, BMI, insulin resistance or IGF-1 levels. However, there was no significant difference in plasma insulin, insulin resistance or ghrelin levels between groups, though PYY declined more rapidly with age but not BMI in PWS subjects. CONCLUSION: Even under the age of 5 years, PWS is associated with low levels of anorexigenic PP, as in older children and adults. Hyperghrelinaemia or hypoinsulinaemia was not seen in these young children with PWS. Change in these appetite hormones was not associated with the timing of the transition to the characteristic hyperphagic phase. However, abnormal and/or delayed development or sensitivity of the effector pathways of these appetitive hormones (for example, parasympathetic and central nervous system) may interact with low PP levels, and later hyperghrelinaemia or hypoinsulinaemia, to contribute to hyperphagia in PWS.

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“…14 By contrast, in a larger and younger study cohort of 40 children and adolescents with PWS (range: 0.2-17.2 years, median age: 3.6 years), ghrelin levels were significantly elevated in the PWS group at any age compared with 84 age and BMI-matched controls. 15 In fact, the highest ghrelin levels in PWS were found in the youngest children. Thus, in their study, the hyperghrelinemia was occurring long before the development of obesity and increased appetite in PWS.…”

Section: Hypogonadismmentioning

confidence: 98%

“…92,93 These recurrent common interstitial deletions measure approximately 5-6 Mb in size and are due to the presence of multiple copies of tandemly repeated sequences at the common breakpoints (BP1, BP2, and BP3) flanking the deleted region. These low copy repeat sequences stretch for approximately 250-400 kb and can cause nonhomologous pairing and aberrant recombination of the 15q11.2-q13 region during meiosis, leading to deletions (causing PWS or AS depending on parental origin), duplications (both maternal and paternal), triplications, and inverted dup (15 can also determine the parental origin in this region and is discussed further below. Although DNA methylation should be a first-line test for diagnosis, it cannot distinguish the molecular class (i.e., deletion, UPD, or ID).…”

Section: Paternal Deletionmentioning

confidence: 99%