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ID
Source
Brief title
Health condition
Brown adipose tissue, insulin resistance, non-shivering thermogenesis, skeletal muscle
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Standard Uptake Values (SUV) of FDG in active BAT, as measured using FDG PET/CT scans (normal-fed period vs. prolonged fasting period);
2. Energy expenditure, as measured using indirect calorimetry, during thermoneutral and mild cold conditions (normal-fed period vs. prolonged fasting period);
3. Skeletal muscle mitochondrial uncoupling, as measured using high-resolution respirometry, in muscle biopsies (normal-fed period vs. prolonged fasting period);
4. Ex vivo skeletal muscle insulin-stimulated glucose uptake, as a measure of insulin sensitivity (normal-fed period vs. prolonged fasting period).
Secondary outcome
1. Skin temperatures and core temperature during thermoneutral and mild cold conditions (normal-fed period vs. prolonged fasting period);
2. Skin perfusion, using Laser Dopller Flowmetry (normal-fed period vs. prolonged fasting period);
3. Blood parameters, among others insulin, glucose, free fatty acids, catecholamines and thyroid hormones, during thermoneutral and mild cold conditions (normal-fed period vs. prolonged fasting period).
Background summary
Brown adipose tissue (BAT) activity is considered an imporant heat-producing mechanism during the process of non-shivering thermogenesis during mild cold exposure. The most common method to measure BAT activity is to measure its glucose uptake rate (by means of FDG PET/CT scanning). Human and animal studies have suggested an important role for insulin and insulin sensitivity in glucose uptake in BAT. We hypothesize that in an insulin resistant state BAT glucose uptake is impaired, causing a decrease in BAT activity.
Study objective
We hypothesise that fasting-induced insulin resistance will result in decreased glucose uptake and activity of brown adipose tissue (BAT). In addition, prolonged fasting will lead to reduced mitochondrial uncoupling in skeletal muscle, which is accompanied by reduced non-shivering thermogenesis.
Study design
Participation will take approximately 64 hours.
Intervention
Volunteers will undergo 2 FDG PET/CT scans of the upper body to determine BAT glucose uptake rate during mild cold exposure. One scan will be performed during a normal-fed period (after 6 hours of fasting). The second scan will be performed after a 55-hour fasting period, which is used to induce an insulin resistant state in otherwise healthy volunteers. To investigate the role of skeletal muscle mitochondrial uncoupling in non-shivering thermogenesis, muscle biopsies will be taken during the normal-fed period and after the prolonged fasting period.
M. Hanssen
Maastricht 6229 ER
The Netherlands
+31 (0)43 3884259
mjw.hanssen@maastrichtuniversity.nl/
M. Hanssen
Maastricht 6229 ER
The Netherlands
+31 (0)43 3884259
mjw.hanssen@maastrichtuniversity.nl/
Inclusion criteria
1. BMI: 18-25 kg/m2;
2. Age: 18-30 years;
3. For females: specific oral contraceptive;
4. Caucasians;
5. Good general health;
6. Sedentary (<2 times/week or <3 hours/week sports).
Exclusion criteria
1. Diabetes mellitus;
2. Elevated fasting blood glucose levels (>5.6 mmol/l);
3. Cardiovascular diseases;
4. Use of beta-blockers;
5. Asthma or other obstructive pulmonary diseases;
6. Hyperthyroidism;
7. For females: pregnancy;
8. Participation in earlier research that included a PET/CT scan;
9. Radiation therapy due to medical treatment.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL3375 |
| NTR-old | NTR3523 |
| Other | METC MUMC / CCMO : 12-3-010 / NL39816.068.12; |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |