Metabol: Cold Induced Futile Cycles In White Adipose Tissue
Study Details
Study Description
Brief Summary
Investigation of futile cycles in white adipose tissue under cold conditions for thermogenesis using two substitutes for glucose metabolism (18F-FDG and 13C-Glucose).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Biopsy without cold induction Participants will undergo a fat biopsy after the first scan, without cooling |
Diagnostic Test: FDG PET/CT
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.
Diagnostic Test: 13C-Glucose injection
0.5 g 13C-Glucose i.v. infusion over 5 minutes, after termination of FDG injection
|
| Other: Biopsy with cold induction Participants will undergo a fat biopsy after the second scan, with cooling |
Other: External cooling
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.
Diagnostic Test: FDG PET/CT
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.
Diagnostic Test: 13C-Glucose injection
0.5 g 13C-Glucose i.v. infusion over 5 minutes, after termination of FDG injection
|
Outcome Measures
Primary Outcome Measures
- Comparison of FDG influx into WAT [2 days]
Comparing the 18F-FDG influx rate (Ki) into the white adipose tissue with and without cold stimulation (intra-individually).
Secondary Outcome Measures
- Quantification of 13C-Glucose metabolites in fat [2 days]
Comparing the 13C-Glucose accumulation in white adipose tissue between Group A (without cold) and B (with cold) stimulation
- Quantification of 13C-Glucose metabolites in blood [2 days]
13C-Lactate concentration in blood samples between Group A (without cold) and B (with cold) stimulation.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Informed Consent as documented by signature
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Healthy participants, as determined by screening assessments and Principal Investigator's judgment
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Health status is defined by the absence of evidence of any active or chronic disease following a medical and surgical history, basic physical examination and blood test
Exclusion Criteria:
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any clinically relevant history or the presence of e.g. respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, psychiatric, metabolic disease, etc.
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Intake of the following medications: Insulin, oral antidiabetic drugs, GLP-1-agonists, Corticosteroids, Sympathomimetic and Sympatholytic drug, Beta-Blocker, Statins.
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BMI > 35 kg/m2
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Resting pulse rate > 70 bpm, resting blood pressure > 130/90 mmHg.
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Serum creatinine > 145 µmol/L
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ASAT> 75 U/L and ALAT > 75 U/L
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γ GT > 100 UI/L and total bilirubin > 30 µmol/l
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Glucose > 7.1 mmol/L
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HbA1c > 46 mmol/mol (>6.4%)
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Intake of anticoagulants or inhibitors of platelet aggregation (e.g. Aspirin, clopidogrel).
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Known tendency to form keloids (hypertrophic scar tissue)
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Known or suspected non-compliance, drug or alcohol abuse,
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Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
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Participation in another study with investigational drug within the 30 days preceding and during the present study
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Participation in another study involving ionizing radiation in the same year
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Previous enrolment into the current study,
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Enrolment of the investigator, his/her family members, employees and other dependent persons
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kantonsspitla Baden | Baden | Aargau | Switzerland | 5404 |
Sponsors and Collaborators
- Kantonsspital Baden
Investigators
- Principal Investigator: Irene A. Burger, MD, Kantonsspital Baden
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Cold exposure of WAT