METABOLIC ADAPTATIONS OF OBESITY WITH GH ADMINISTRATION

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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. In the United States, the prevalence of obesity has reached alarming and even epidemic proportions. Despite the billions of dollars spent annually on weight-loss related products more than 50 million Americans are either overweight or obese. Growth hormone (GH) and insulin are primary regulators of protein synthesis, as well as lipid and glucose metabolism. Serum GH is reduced in obese subjects primarily as a result of reduced GH pulse amplitude. Thus, GH secretion in obese individuals is not only decreased in absolute terms but the pattern of GH presentation to the peripheral tissues is changed from a highly pulsatile one to absence of pulsatile GH secretion, i.e resembling a low rate constant infusion. The pattern of GH secretion has been shown to be an independent factor in the regulation of liver and bone metabolism. Thus a similar role of GH pulsatility may also be of importance of regulating energy distribution whereby different patterns of GH presentation to the peripheral tissues playing divergent roles in selective metabolic activities of fat and protein. The impairment in GH secretion is due to the excess of visceral fat. It is not clear whether administration of GH will increase lipolytic(breakdown of fat) rate or whether mode of administration of GH alters lipolysis. A single infusion of GH stimulates muscle protein synthesis, whereas more prolonged administration reduces urinary urea excretion and increases whole body protein synthesis. Administration of GH diminishes protein breakdown and promotes lean body mass with time. We propose to study whether giving Growth hormone as continuous vs. pulsatile infusion will have differential effects on protein synthesis, lipolysis, glucose uptake and insulin sensitivity involved in regulating fuel metabolism in muscle. We will study 24 obese subjects. They will be admitted to GCRC for 9 days in total over 2 visits. They will be studied with special metabolic tests during continuous or pulsatile GH infusion administration . The effects on metabolism will be evaluated by blood tests following infusions of fat, glucose and protein and response of muscles will be evaluated with muscle biopsy. The results of this study will pave the way for better understanding of the role of GH in metabolic adaptation in obese subje