Cold Induced Activation of Brown Adipose Tissue in Humans

Study Overview
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Brief Summary
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This study investigates cold-induced brown fat activation assessed using PET/MR scans. Subjects will participate in an acute cooling intervention day and a thermoneutral intervention day with PET/MR scans on both days. A secondary purpose is to make a validation of an infrared thermography camera by comparison of skin temperatures and SUV of the supraclavicular brown adipose tissue.

Detailed Description
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The field of human brown adipose tissue (BAT) research is focused on activation of BAT as a means of manipulating energy expenditure and potentially anti-obesity and anti-diabetic properties of the tissue. This is well established in rodent studies and explained as due to the specific brown fat uncoupling protein 1 (UCP1). Despite increasing evidence that indicates a metabolic regulatory role of BAT in humans, BAT activation/recruitment is not fully understood and even less is known about the endocrine capacities of human BAT. Cold induced brown fat activity will be assessed with PET/MR scans and validate an infra-red thermography camera, as well as perform a proteomic screening using blood samples under these two intervention days. 15 healthy lean male subjects will serve as their own control in a cross-over randomized control study, including a pre-examination day, a thermoneutral-day and a cooling test-day with cold exposure followed by a PET/MR scan to determine BAT activity. An extra cooling day is applied for the external validation of the infrared thermography camera. Blood samples and abdominal fat-biopsies will be taken at thermoneutral condition and under cold stimulation of brown fat.

Official Title
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Cold Induced Activation of Brown Fat in Humans Assessed With PET/MR Scans and Skin-temperature Measure - A Cross-over Randomized Controlled Trial.

Conditions
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BAT, Adipose Tissue, Brown, Brown Adipose Tissue, Brown Fat, Uncoupling Protein 1, Adipokines, Proteomics, Infrared Thermography, Obesity, Type 2 Diabetes, Proteins

Intervention / Treatment
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* Procedure: Cooling
* Procedure: Thermoneutral


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-30 years. Men Caucasian white Body Mass Index 19-25 kg/m2. Moderate physical activity level (not more than 8-10 hours of training pr. Week) Ability to give informed consent. Ability to follow verbal and written instructions in Danish. Body fat percent under 21% measured at the pre-examination day. Exclusion Criteria: Chronic diseases: Hormonal: Metabolic Diseases mb. Graves, hypothyroidism, myxedema and goiter. Diabetes Melitus, Coronary heart disease (history of myocardial infarction, unstable angina pectoris, or congestive heart failure), cancer treated within last 3 years. Tobacco, marijuana or intravenous drug use within 1 year of screening. Dieting, recent weight loss (>3 kg within 3 month) or a history of an eating disorder. Dietary supplements. History of depression, psychosis, or other psychiatric illness requiring hospitalization. Alcohol consumption >14 units/week. History of alcohol abuse within the past 3 years. Known liver disease or elevated liver biomarkers more than 2 times upper normal levels in the preliminary investigation. Known kidney disease or elevated kidney biomarkers, eCRF <60 ml/min, in the preliminary investigation. Use of daily medications, except for seasonal use of antihistamines. Diagnosed sleep disturbances. Pacemaker or other electronics implanted in the body. Magnetic impressionable metal implants or foreign objects in the body inconsistent with completion of MR. Claustrophobia Communication problems, including understanding the experimental protocol History of contrast allergy. Winter swimmers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cooling<br>Individualized cooling protocol. | Procedure: Cooling<br>* Individualized cooling protocol.<br>* Other names: Cold activation of BAT;|
| Experimental: Thermoneutral<br>Thermoneutral condition day. | Procedure: Thermoneutral<br>* Thermoneutral control day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in brown adipose tissue (BAT) activity after cooling versus no cooling. | BAT activity is measured by standard fluorodeoxyglukose uptake volume (SUV mean) in the supraclavicular BAT depot using PET/MR scans. Difference between scans performed after 2 hours of cooling and 2 hours of no cooling is calculated. | Difference in SUV mean after 2 hours of cooling versus 2 hours of no cooling. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in BAT activity after cooling versus no cooling. | BAT activity is measured by skin temperature in the supraclavicular BAT depot using infrared thermography imaging. Difference between peak temperature change (peak temperature minus baseline temperature) during 2 hours of cooling and 2 hours of no cooling is calculated. | Difference in peak temperature after 2 hours of cooling versus 2 hours of no cooling. | 
| Difference in resting energy expenditure after cooling versus no cooling | Difference in resting energy expenditure after cooling versus no cooling, measured as mean difference in KJ/min. | Difference in resting energy expenditure after 2 hours of cooling versus 2 hours of no cooling. |