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The Relationship Between Body Composition and Growth Hormone, SIRT Signaling, Protein Turnover and Insulin Sensitivity

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ClinicalTrials.gov Identifier: NCT01299831
Recruitment Status : Completed
First Posted : February 18, 2011
Last Update Posted : May 26, 2014
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of this study is to investigate signaling pathways in fat and muscle, as well as turnover of protein, sugar and fat after stimulation with growth hormone and during fasting in lean and obese subjects. This will help clarify differences in the human metabolism between lean and obese subject and provide us with a better understanding of the molecular mechanisms regulating the basic metabolism during prolonged fasting.

Condition or disease Intervention/treatment
Healthy Behavioral: 72 hour fast Behavioral: control, 12 hour fast Drug: Growth hormone Drug: Olbetam

Detailed Description:

In an evolutionary context, it is likely that "inherited" obesity provides a survival advantage when there are shortages of food, but also increases the risk of lifestyle diseases in times of prosperity. This may explain the high incidence of obesity, diabetes and cardiovascular disease in the western world today. Obese individuals have high levels of free fatty acids (FFAs) in the blood and FFAs are both protein sparing (giving an evolutionary survival advantage) but also cause increased insulin resistance (which increases the risk of diabetes and cardiovascular disease). Obesity also leads to low growth hormone (GH)-levels, whereas fasting is accompanied by high GH- and FFA-levels and increased IGF-I mRNA in muscle. It is likely that obese individuals are more capable of fasting than lean individuals and will lose less protein during fasting, have increased activation of GH signaling and altered activation of other signaling proteins. And obese individuals are likely to be more sensitive to growth hormone than lean individuals based on FFA-responses, intracellular signaling, protein loss and insulin sensitivity.

We would like to test 3 hypotheses: (1) Obese individuals are more capable of fasting than lean individuals and will lose less protein during fasting (2) Activation of lipolysis is an important prerequisite for limiting protein loss during fasting in both slim as obese individuals. (3) Obese individuals are more sensitive to growth hormone than lean individuals based on FFA responses and activation of intracellular signals. The hypotheses are tested in 8 lean and 8 obese healthy young men, who are studied 4 times: (i) after 12 hours of fasting (ii) after 72 hours of fasting (iii) after GH-bolus (0.005 mg/kg over 20 min.) and (iv) after 72 hours of fasting with inhibition of fat metabolism (tablet acipimox 250 mg every 4 hours) during the last 12 hours of fasting and during the study period.

Each study period consists of a 4-hour basal period and a 2 hour hyperinsulinemic euglycemic clamp (30 mU/m2/min). Muscle- and fat-biopsies are taken and analyzed for enzyme expression and activation of various signaling pathways. The study subjects are given glucose-, amino acid-, urea- and palmitate-tracers and specific hormones and metabolites are measured for assessment of underlying molecular mechanisms regulating the basic human energy metabolism.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: THE RELATIONSHIP BETWEEN BODY COMPOSITION AND GROWTH HORMONE, SIRT SIGNALING, PROTEIN TURNOVER AND INSULIN SENSITIVITY. Studies of Signaling Pathways in Fat and Muscle, and Turnover of Protein, Sugar and Fat After Stimulation With Growth Hormone and During Fasting in Lean and Obese Subjects
Study Start Date : January 2011
Primary Completion Date : December 2013
Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: 72 hour fast Behavioral: 72 hour fast
The participants will be fasting 72 hours prior to the start of the study day, drinking water is allowed.
Experimental: 12 hours fast Behavioral: control, 12 hour fast
The 12 hour fast will be used as a basic metabolic control
Experimental: 12 hour fast, growth hormone bolus Drug: Growth hormone
Genotropin bolus(0,005 mg/kg over 20 min.) will be administered at the beginning of the study day after a 12 hour fast.
Experimental: 72 hour fast, inhibition of lipolysis Drug: Olbetam

The participants will be fasting 72 hours prior to the start of the study day, drinking water is allowed.

During the last 12 hours of fasting and the study day lipolysis will be inhibited with one tablet of olbetam 250 mg every 4 hours.



Outcome Measures

Primary Outcome Measures :
  1. Measurements of changes in metabolism [ Time Frame: 6 hours ]
    Measurements of the switch to lipid metabolism during fasting in lean and obese human subjects.


Secondary Outcome Measures :
  1. Signaling pathways in muscle and fat tissue involved in regulation of metabolism [ Time Frame: 6 hours ]
    Protein and gene-exspression, phosphorylation and acetylation of specific proteins involved in lipid-, glucose and protein metabolism.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • healthy lean (BMI19-25) and healthy obese (BMI 32-40) men
  • written consent before study start

Exclusion Criteria:

  • known medical conditions
  • any medication
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01299831


Locations
Denmark
Department of medical endocrinology, University Hospital of Aarhus
Aarhus, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Aarhus University Hospital
More Information

Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT01299831     History of Changes
Other Study ID Numbers: M-2010082
First Posted: February 18, 2011    Key Record Dates
Last Update Posted: May 26, 2014
Last Verified: May 2014

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Hormones
Insulin
Acipimox
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Hypoglycemic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents