Macronutrient Regulation of Ghrelin and Peptide YY
Condition: Obesity; Prader Willi Syndrome
MeSH terms: Prader-Willi Syndrome; Obesity; Syndrome
Study type: Interventional

Summary: 
      The hyperghrelinemia of children with PWS provides a unique model by which to explore the
      hormonal and metabolic effects of orexigenic hormones in normal and pathologic conditions. An
      important question to be addressed by this proposed research includes the macro-nutrient
      regulation of ghrelin and PYY in obese children and children with PWS. As ghrelin antagonists
      are considered potential future anti-obesity agents, it is essential to gain understanding of
      the developmental, nutritional and hormonal regulation of this important orexigenic hormone
      in children.
    

Detailed description: 
      Obesity continues to be a prevalent health concern affecting every race of the American
      population. Studies show that obese children are likely to become obese adults. Also, recent
      studies report significant years of life lost due to the impact of being an obese adult .
      Thus, insights into the pathogenesis of childhood obesity and preventative measures are
      needed to combat the inevitable increase in worldwide incidence of obesity and its associated
      co-morbidities.

      Ghrelin is a 28 amino acid acylated peptide which is an endogenous ligand of the growth
      hormone secretagogue receptor (GHS-R), a hypothalamic G-protein-coupled receptor.
      Enteroendocrine cells (X/A-like cells) of the stomach are the major site of ghrelin
      synthesis, although a minor proportion of ghrelin synthesis occurs in other sites such as the
      hypothalamus, pituitary, duodenum, jejunum and lung. Secreted in response to meals, ghrelin
      stimulates feeding through activation of anabolic neurons in the hypothalamic arcuate nucleus
      that co-express neuropeptide Y (NPY) and agouti-related protein (Agrp). Ghrelin relays its
      information from the GI tract to specific nuclei in the hypothalamus via the gastric afferent
      vagal nerve.

      Studies in rodents support the premise that ghrelin is involved in energy balance. In humans,
      physiological levels of ghrelin influence energy homeostasis in humans.The rise in plasma
      ghrelin concentrations during fasting may play a role in meal initiation and body weight
      regulation.

      Nearly all other forms of obesity are associated with low ghrelin levels. Paradoxically,
      researchers discovered that ghrelin levels in adults and children with PWS are 3-5 times
      higher than those in age- and BMI-matched controls. Hyperghrelinemia may thus play a causal
      role in the hyperphagia and obesity of PWS.

      The hyperghrelinemia of children with PWS provides a unique model by which to explore the
      hormonal and metabolic effects of orexigenic hormones in normal and pathologic condtions. An
      important question to be addressed by this proposed research includes the macro-nutrient
      regulation of ghrelin in normal children and children with PWS. As ghrelin antagonists are
      considered potential future anti-obesity agents, it is essential to gain understanding of the
      developmental, nutritional and hormonal regulation of this important orexigenic hormone in
      children.
    

Intervention name(s): High carbohydrate meal; High fat meal
Intervention type(s): Other; Other
Intervention description(s): 65% carbohydrate, 17% protein, and 18% fat; 58% fat, 17% protein, and 25% carbohydrate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Obesity; Orexigen; Insulin; Leptin; Adiponectin; Growth hormone replacement