Growth Hormone as a Determinant of Weight Regulation
| Status: | Completed |
|---|---|
| Conditions: | Obesity Weight Loss |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 35 |
| Updated: | 4/21/2016 |
| Start Date: | September 2005 |
| End Date: | December 2015 |
Growth Hormone as a Determinant of Weight Regulation.
With the alarming increase in the prevalence of obesity, identifying factors that predispose
individuals to weight-gain is of critical importance. Even when caloric intake and physical
activity levels are well controlled, susceptibility for weight-gain is heterogeneous. Basal
metabolic rate (BMR) represents the largest portion of daily energy expenditure in normal
adults, and as such, variability in BMR among individuals can be a major factor in
determining the susceptibility for gaining weight. However, factors responsible for this
variability in BMR and resistance to weight-gain remain unclear. Our preliminary data
indicate that high-normal growth hormone (GH) concentration is associated with resistance to
weight-gain in rats when overfed and greater weight-loss in humans when underfed. In
addition, the investigators have found that the pulsatility of GH secretion has profound
effects on several metabolic processes. Therefore, together these findings suggest that
endogenous GH secretion is associated with body weight regulation, and the pulsatility (peak
amplitude) of GH secretion, rather than the absolute GH concentration, per se, may be
responsible for this effect. Because GH influences many of the key metabolic processes that
contribute to BMR (e.g.; protein synthesis, proteolysis, substrate cycling), the
investigators anticipate that the resistance to weight-gain in persons with elevated GH
concentrations will be associated with an increase in BMR due to acceleration of some or all
of these processes. Our overall hypothesis is that increased GH secretion can protect
against weight-gain due to an augmentation of major metabolic processes that contribute to
BMR. Identifying factors responsible for predisposing individuals to weight-gain will lead
to establishing improved methods for reducing the prevalence of obesity.
individuals to weight-gain is of critical importance. Even when caloric intake and physical
activity levels are well controlled, susceptibility for weight-gain is heterogeneous. Basal
metabolic rate (BMR) represents the largest portion of daily energy expenditure in normal
adults, and as such, variability in BMR among individuals can be a major factor in
determining the susceptibility for gaining weight. However, factors responsible for this
variability in BMR and resistance to weight-gain remain unclear. Our preliminary data
indicate that high-normal growth hormone (GH) concentration is associated with resistance to
weight-gain in rats when overfed and greater weight-loss in humans when underfed. In
addition, the investigators have found that the pulsatility of GH secretion has profound
effects on several metabolic processes. Therefore, together these findings suggest that
endogenous GH secretion is associated with body weight regulation, and the pulsatility (peak
amplitude) of GH secretion, rather than the absolute GH concentration, per se, may be
responsible for this effect. Because GH influences many of the key metabolic processes that
contribute to BMR (e.g.; protein synthesis, proteolysis, substrate cycling), the
investigators anticipate that the resistance to weight-gain in persons with elevated GH
concentrations will be associated with an increase in BMR due to acceleration of some or all
of these processes. Our overall hypothesis is that increased GH secretion can protect
against weight-gain due to an augmentation of major metabolic processes that contribute to
BMR. Identifying factors responsible for predisposing individuals to weight-gain will lead
to establishing improved methods for reducing the prevalence of obesity.
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, the investigators
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. The investigators will
measure basal 24h GH secretion and BMR in 106 non-obese men and women. The investigators
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
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].
The investigators 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.
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, the investigators
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. The investigators will
measure basal 24h GH secretion and BMR in 106 non-obese men and women. The investigators
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
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].
The investigators 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.
Inclusion Criteria:
Age = 21-35 years Weight stable (< ± 5 pound over past 6 months) Premenopausal (women
only) Body mass index 18 - 26 kg/m2 Must be willing to be randomized to receive GH
infusion during 2 week Michigan Clinical Research Unit (MCRU) visit
Exclusion Criteria:
- Evidence of metabolic or cardiovascular disease Pregnancy (women only) Hyperlipidemia
(fasting plasma triglyceride concentration > 150 mg/dl) Hematocrit < 34% Liver
Function test abnormalities participating in a regular exercise program (> 2 h/week)
taking any prescription medication (except birth control)
We found this trial at
1
site
University of Michigan The University of Michigan was founded in 1817 as one of the...
Click here to add this to my saved trials
