This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Prader-Willi Syndrome PWS is a neurobehavioral syndrome whose clinical features include neonatal failure-to-thrive, a distinct behavioral phenotype, cognitive impairment, hypotonia, hyperphagia and obesity. Their hyperphagia increased hunger; reduced satiation meal termination and reduced satiety prevention of meal initiation arise from altered brain development and function, which is a consequence of the genetic alterations that characterize this condition. This study will elucidate the neuroanatomical correlates of hunger and satiety using functional MRI fMRI in PWS and other obese patients, and lean subjects, before and after ingestion of a meal.Food ingestion reduces hunger and induces satiety preventing meal initiation through post-prandial changes in circulating metabolites and hormones, which alter activity in brain regions involved in motivation, reward and arousal. Defects in these pathways in PWS and obesity lead to excess caloric intake. We hypothesize that the usual suppression of reward and arousal responses to food stimuli in the fed versus fasted state is reduced in PWS subjects due to abnormal brain development, and also reduced in non-PWS obese subjects. We further hypothesize that this suppression is induced by ingestion of larger meals. These hypotheses investigated with studies performed in patients with PWS and age- and sex-matched lean and obese controls before and after ingestion of mixed meals of different caloric loads, in order to produce fasted and differentially sated states. We will examine fMRI activation in response to viewing food pictures, measure appetite with test meals and visual analogue scales, and correlate the observed changes with circulating hormones.
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