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Feeding and Satiety Signals in Prader-Willi Syndrome: Relation to Obesity, Diet, and Behavior

  • Maithe Tauber
  • Emmanuelle Mimoun
  • Patrick Ritz
  • Gwenaelle Diene
Chapter

Abstract

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder that arises from lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. PWS has been classically described as having two nutritional phases, but detailed descriptions recently led to the characterization of four main nutritional phases, with a particular emphasis on the fact that excessive weight gain occurs prior to hyperphagia. Patients with PWS show reduced satiety and early return of hunger. They are prone to eating nonfood items (pica) or contaminated foods, and to combine foods inappropriately. The abnormal feeding behavior in PWS includes a morbid obsession with food, food stealing, hoarding, and foraging. Evaluation of eating behavior has not yet been standardized in PWS, but questionnaires are being validated and this will enable caregivers to better characterize certain features of the syndrome, such as satiety and hyperphagic behavior, drive, and severity. PWS has been described as a genetic hypothalamic syndrome, because it includes hyperphagia as well as temperature dysregulation, sleep-wake cycles abnormalities, and metabolic and endocrine disorders. Recent data also suggest more complex dysfunctions involving the corticolimbic areas. In any case, the most striking and specific defects in PWS feeding and satiety signals is the high circulating level of the orexigenic stomach-derived hormone ghrelin and the decreased level of pancreatic polypeptide. Hypergrhelinemia could explain the obesity and the GH deficiency. Interestingly, these two main abnormal signals may explain the major feeding disturbances described in individuals with PWS. Part of their action requires an intact vagal nerve reflex and they both regulate gastric emptying. These findings suggest that the eating behavior of people with PWS may be due to decreased satiety rather than to increased hunger. Recent functional MRI findings suggest that hyperphagia may be linked to at least two mechanisms involving limbic and paralimbic regions that drive eating behavior (e.g., the amygdala) and regions that regulate food intake (e.g., the medial PFC). Management of PWS involves strict and permanent environmental control with early institution of a low-calorie, well-balanced diet, with regular exercise, rigorous supervision, restriction of access to food and money, with consideration of legal and ethical obligations, and appropriate psychological and behavioral counseling for the patient and family. The effects of GH treatment on hyperphagia remain to be demonstrated, but GH prevents the increase in BMI and the decrease in lean-body mass observed in patients without treatment.

Keywords

Anorexia Nervosa Ghrelin Level Pancreatic Polypeptide Plasma Ghrelin Level Acylated Ghrelin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AgRP

Agouti-Related Peptide

AP

Area Postrema

ARC

Arcuate Nucleus

BBB

Blood Brain Barrier

BMI

Body Mass Index

CNS

Central Nervous System

DMH

Dorsomedial Hypothalamus

FISH

Fluorescence In Situ Hybridization

fMRI

Functional MRI

FTT

Failure to Thrive

GH

Growth Hormone

GHR

Ghrelin Receptor

GnRH

Gonadotrophin Releasing Hormone

IQ

Intelligence Quotient

mPFC

Medial Prefrontal Cortex

MRI

Magnetic Resonance Imaging

NA

Nucleus Accumbens

NPY

Neuropeptide Y

NTS

Nucleus Tractus Solitarius

OFC

Orbitofrontal Cortex

OXM

Oxyntomodulin

PFC

Pre Frontal Cortex

PP

Pancreatic Polypeptide

PVN

Paraventricular Nucleus

PWS

Prader-Willi Syndrome

PYY

Peptide YY

UPD

UniParental Disomy

VMH

Ventromedial Hypothalamus

VTA

Ventral Tegmental Area

VTA

Ventral Tegmental Area

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Maithe Tauber
    • 1
  • Emmanuelle Mimoun
  • Patrick Ritz
  • Gwenaelle Diene
  1. 1.Centre de référence du syndrome de Prader-WilliHôpital des EnfantsToulouse Cedex 9France

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