Healthy
Conditions
Brief summary
Background: Calorie restriction increases longevity in many species and attenuate the development of chronic disorders including type 2 diabetes, cardiovascular diseases and cancer. In mice reduced activity of insulin-like growth factor I (IGF-I) and/or insulin is associated with extended longevity. Growth hormone (GH) is the main regulator of IGF-I production, but the molecular mechanism whereby GH switches from IGF-I stimulation (protein anabolism) to fatty acid oxidation (fatty acid catabolism) as well as induction of insulin resistance during fasting remains enigmatic. Hypotheses: The changes of the global set of metabolites, induction of insulin resistance, and the shift in metabolism from protein anabolism to lipolysis together with the potentially favorable effect of calorie restriction during fasting depend on preserved fasting-induced GH secretion. Aim: The investigators wish to provide knowledge on changes in metabolites and shift in signaling pathways that take place at the transition to the fasting state among healthy overweight and obese subjects. Furthermore the investigators wish to determine the effect of GH on the adaption of the metabolism to a fasting state.
Interventions
OTHERFasting
72 hours of fasting
DRUGSaline
Concomitant saline during fasting
DRUGPegvisomant
Concomitant Growth hormone receptor blockade with Pegvisomant during fasting
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
20 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy men * written consent * body mass index (BMI) 25-40 * age 20-60 years
Exclusion criteria
* any kind of disease * regular medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin and growth hormone signaling, expressed as CHANGE in phosphorylation of intracellular target proteins and CHANGE in messenger ribonucleic acid (mRNA) expression of target genes in muscle- and fat-tissue. | Muscle and fat biopsies obtained at t1= 9.00 am (60 min) and t2=12.30 am (270 min) on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days) | Change in phosphorylation of target proteins and mRNA expression of target genes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose metabolism | Change in glucose metabolism using glucose tracer from t=0 min - 360 min on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days) | Change in glucose metabolism assessed by tracer kinetics on every study day and by indirect calorimetry. |
| Magnetic resonance (MR) spectroscopy | During fasting: t= 12 hours and t= 48 hours of fasting | — |
| Change in concentrations of metabolites in the insulin and growth hormone signaling pathways using metabolomics | Muscle-tissue obtained at t1= 9.00 am (60 min) and t2=12.30 am (270min) on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days) | Method: Metabolomics |
| Fat metabolism | Change in fat metabolism using palmitic acid tracer from t1=180 min - 240 min and t2=300 min - 360 min on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days) | Change in fat metabolism assessed by tracer kinetics on every study day and by indirect calorimetry. |
| Protein metabolism | Change in protein metabolism using urea tracer from t=0 min - 240 min on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days) | Change in protein metabolism assessed by tracer kinetics on every study day and by indirect calorimetry. |
Countries
Denmark
Outcome results
None listed