Cold Induced Futile Cycles In White Adipose Tissue

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.

Inclusion criteria

• Informed Consent as documented by signature
• Healthy participants, as determined by screening assessments and Principal Investigator's judgment
• 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

• any clinically relevant history or the presence of e.g. respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, psychiatric, metabolic disease, etc.
• Intake of the following medications: Insulin, oral antidiabetic drugs, GLP-1-agonists, Corticosteroids, Sympathomimetic and Sympatholytic drug, Beta-Blocker, Statins.
• BMI > 35 kg/m2
• Resting pulse rate > 70 bpm, resting blood pressure > 130/90 mmHg.
• Serum creatinine > 145 µmol/L
• ASAT> 75 U/L and ALAT > 75 U/L
• γ GT > 100 UI/L and total bilirubin > 30 µmol/l
• Glucose > 7.1 mmol/L
• HbA1c > 46 mmol/mol (>6.4%)
• Intake of anticoagulants or inhibitors of platelet aggregation (e.g. Aspirin, clopidogrel).
• Known tendency to form keloids (hypertrophic scar tissue)
• Known or suspected non-compliance, drug or alcohol abuse,
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Participation in another study with investigational drug within the 30 days preceding and during the present study
• Participation in another study involving ionizing radiation in the same year
• Previous enrolment into the current study,
• Enrolment of the investigator, his/her family members, employees and other dependent persons