EFFECTS OF GROWTH HORMONE ON METABOLISM AND SATIATION IN PRADER-WILLI SYNDROME

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Prader-Willi Syndrome (PWS) is a complex neurobehavioral syndrome whose clinical features include neonatal failure-to-thrive, a distinct behavioral phenotype, cognitive impairment, hypotonia, hyperphagia and morbid obesity. This syndrome is the most commonly recognized genetic cause of obesity. It has been suggested that the hyperphagia is secondary to altered hypothalamic function, which is a consequence of the genetic alterations that characterize this condition. Children with Prader-Willi syndrome have evidence of a growth hormone (GH) deficiency secondary to hypothalamic dysfunction 3. Studies have shown that children with Prader-Willi syndrome treated with GH have a decrease in fat mass and an increase in lean body mass, as well as an increase in growth velocity and in resting energy expenditure 26,24. It is currently unknown, however, if treatment of children with Prader-Willi syndrome with GH causes changes in the hypothalamus, or if the effects are solely peripheral1. This study will investigate the beneficial effects of GH on hypothalamic recognition of hunger and satiety, as well as on the basal metabolic rate and body composition of PWS individuals. We will compare the neuroanatomical correlates of hunger and satiation using functional MRI (fMRI) on PWS patients before and one year after GH treatment. In addition, we will use normal weight siblings and non-PWS obese individuals as additional comparison groups. Blood will be drawn to determine various hormonal and neurotransmitter levels at times correlating with hunger and satiety in these individuals. Basal metabolic rate (BMR) and body composition via dual energy X-ray absorptiometry (DEXA) will be assessed for all individuals, and will be reevaluated in PWS subjects one year after treatment with GH.