Obesity
Conditions
Keywords
Adipose Tissue, Brown
Brief summary
This study investigates the significance of adenosine and A2A receptors in human brown adipose tissue (BAT) in vivo. Using positron emission tomography (PET), perfusion and the density of A2A receptors will be measured in supraclavicular BAT and other tissues in healthy men. The investigators hypothesize, that adenosine can activate BAT, and that adenosine A2A receptor density changes when BAT is activated by cold exposure. Understanding the mechanisms of BAT activation and the role of endocannabinoids in humans is important and beneficial in fighting against the epidemic of obesity and diabetes.
Detailed description
Adenosine is a purine nucleoside released locally in BAT when noradrenaline and ATP are released from sympathetic nerves. Recently it was found that adenosine activates murine and human brown adipocytes, and recruits beiging of white fat via adenosine A2A receptors (A2AR). Furthermore, studies with mice have shown improvements in glucose homeostasis after administration of A2AR agonists. In this study the investigators use the PET radiotracer \[15O\]-H2O to quantify perfusion of BAT, white adipose tissue (WAT) and muscle in three conditions: room temperature, cold exposure and intravenous infusion of adenosine. Another PET radiotracer \[11C\]TMSX is used to quantify adenosine A2A receptor density of BAT, WAT and muscle in room temperature and during cold exposure.
Interventions
DRUGAdenosine
Intravenous infusion of adenosine (0.14 mg/kg) is administered for 5 minutes during PET/CT scan.
OTHERCold exposure
Controlled cold exposure is performed before and during PET/CT scan.
Sponsors
University of Bonn
Turku University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Each subject participates in PET/CT scans in room temperature conditions, during cold exposure and during i.v. infusion of adenosine.
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male sex 2. BMI 20 - 28 kg/m2 3. Age: 18- 40 years 4. Normal OGTT 5. Healthy, no regular medication
Exclusion criteria
1. BMI \< 20 kg/m2 or BMI \> 28 kg/m2 2. Low or high blood pressure 3. Asthma or other obstructive lung disease 4. Sick sinus syndrome, prolonged QT-interval, or any heart disease 5. Any chronic disease that could affect the study outcome, including diabetes 6. Mental disorder or poor compliance 7. Eating disorder or excessive use of alcohol, tobacco smoking or drug use 8. Past dose of radiation 9. Any other condition that in the opinion of the investigator could create a hazard to the subject safety, endanger the study procedures or interfere with the interpretation of study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BAT perfusion | Effect within 10 minutes | Perfusion of BAT with \[15O\]-H2O PET-CT |
| A2A receptor density in BAT | Effect within 3 hours | Density of A2A receptors in BAT measured with \[11C\]-TMSX PET/CT |
Outcome results
None listed