• basal metabolic rate [ Time Frame: 20-30 min ] [ Designated as safety issue: No ]
  
• growth hormone [ Time Frame: 24h ] [ Designated as safety issue: No ]
  
• changes in body weight and body composition [ Time Frame: 2 weeks (weight gain) and 4 weeks (weight loss) ] [ Designated as safety issue: No ]
  
• whole body protein turnover [ Time Frame: 4h ] [ Designated as safety issue: No ]
  
• muscle and liver protein synthesis [ Time Frame: 6h ] [ Designated as safety issue: No ]
  
• lipolytic rate [ Time Frame: 1h ] [ Designated as safety issue: No ]
  
• fatty acid/triglyceride cycling [ Time Frame: 1h ] [ Designated as safety issue: No ]
  

Other: overfeeding
overfeeding 2000kcals/day above energy requirements for 14d
Drug: growth hormone administration
growth hormone administrated for 2 weeks (dose = 1.0 mg/m2/d)
Procedure: caloric restriction/weight loss
underfeed 700kcal/day below energy requirements for 4 wks

The susceptibility to gain weight is highly variable even when caloric intake and physical activity are well controlled. Because basal metabolic rate (BMR) represents ~70% of total daily energy expenditure (TDEE), even a small difference in BMR can affect daily energy balance, thereby increasing the susceptibility for gaining weight. Our preliminary data indicate that high-normal growth hormone (GH) secretion is associated with resistance to weight-gain in rats when overfed and greater weight-loss in humans when underfed. Given that GH influences many of the key metabolic processes that contribute to BMR, we hypothesize that persons with high-normal GH will be resistant to weight-gain because of a high BMR, resulting from accelerated rates of these processes. We will measure basal 24h GH secretion and BMR in 106 non-obese men and women. We will also measure protein synthesis, proteolysis, triglyceride/fatty acid cycling (all measured using stable isotope tracer methods) to determine the relationships among these processes, BMR, and GH [Specific Aim 1]. Subjects identified as having "low-normal" (<1.5 ug/L) and "high-normal" (>3 ug/L) 24h GH will then be admitted to the hospital for a 2 wk overfeeding protocol (~2000 kcal/d >TDEE - with restricted physical activity), immediately followed by a 4 wk caloric restriction protocol (~750 kcal/d <TDEE) to compare changes in weight, body composition and intra-abdominal adiposity between these groups that differ markedly in their GH secretion (GH measured before the diet) [Specific Aim 2]. A subset of subjects with low-normal GH will receive intravenous GH throughout the 2 wk overfeeding period at either: 1. a constant rate or 2. as a pulsatile infusion (to mimic endogenous secretion). BMR will be assessed daily and protein synthesis, proteolysis, and triglyceride/fatty acid cycling will be measured at the end of the 2 wks [Specific Aim 3]. We anticipate that a higher GH pulsatility (peak amplitude), rather than elevated GH concentration, per se, will increase protein synthesis, proteolysis, and triglyceride/fatty acid cycling with a resultant increase in BMR and resistance to weight-gain. Identifying factors responsible for predisposing individuals to weight-gain will help combat the alarming rise in the prevalence of obesity.