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Investigation of futile cycles in white adipose tissue under cold conditions for thermogenesis using two substitutes for glucose metabolism (18F-FDG and 13C-Glucose).
Thermogenesis is defined as a process, which generates heat by the depletion of energy-rich molecules. Evolutionary, it is an essential process that allows the survival at lower temperatures. Since the discovery of brown adipose tissue (BAT) it is believed that this part of the adipose tissue can dissipate energy for heat thanks to the uncoupling protein 1 (UCP1). Since energy expenditure is increased as a consequence of thermogenesis, pharmacological induction of this pathway presents an interesting therapeutic target to counter obesity. However, recent investigations indicate that white adipose tissue (WAT) is much more versatile and probably essentially indispensable for thermogenesis.
To investigate the mechanism of this futile cycle in WAT we plan to investigate the glucose metabolism in 24 healthy volunteers with 2 exams (one with and one without external cooling) with two substitutes for glucose. We will use 18F-FDG to quantify the glucose influx into WAT using dynamic PET/CT scans and 13C-Glucose to analyze the downstream metabolites.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Biopsy without cold induction | Other | Participants will undergo a fat biopsy after the first scan, without cooling |
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| Biopsy with cold induction | Other | Participants will undergo a fat biopsy after the second scan, with cooling |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| External cooling | Other | water-circulating cooling/warming sleeves connected to a medical cooling device (Hilotherm Clinic®, Hilotherm GmbH, Germany) will be placed around the subject's abdomen and lower back. Initially the temperature of the water will be set to 25°C. A mild cold stimulus will be applied by reducing the temperature of the circulating water by approximately 1°C every 2 minutes to a minimum of 10°C. |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of FDG influx into WAT | Comparing the 18F-FDG influx rate (Ki) into the white adipose tissue with and without cold stimulation (intra-individually). | 2 days |
| Measure | Description | Time Frame |
|---|---|---|
| Quantification of 13C-Glucose metabolites in fat | Comparing the 13C-Glucose accumulation in white adipose tissue between Group A (without cold) and B (with cold) stimulation | 2 days |
| Quantification of 13C-Glucose metabolites in blood |
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Inclusion Criteria:
Exclusion Criteria:
Only male volunteers
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| Name | Affiliation | Role |
|---|---|---|
| Irene A. Burger, MD | Kantonsspital Baden | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kantonsspitla Baden | Baden | Canton of Aargau | 5404 | Switzerland |
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| ID | Term |
|---|---|
| D008659 | Metabolic Diseases |
| ID | Term |
|---|---|
| D009750 | Nutritional and Metabolic Diseases |
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Non blinded, randomised, open label
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| FDG PET/CT | Diagnostic Test | o 75 MBq 18F-FDG will be injected through the intravenous line on the scanner manually (bolus injection) with a simultaneous start of dynamic FDG-PET/CT scan for 45 minutes and a partial body scan from head to the abdomen after 45 minutes. Total scan time 60 minutes. |
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| 13C-Glucose injection | Diagnostic Test | 0.5 g 13C-Glucose i.v. infusion over 5 minutes, after termination of FDG injection |
|
13C-Lactate concentration in blood samples between Group A (without cold) and B (with cold) stimulation.
| 2 days |