Neural representations of hunger and satiety in Prader–Willi syndrome

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 (mean±s.d. age=29±6; BMI=31.5±5.1; IQ=71±8, 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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