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…
ID
Bron
Verkorte titel
Aandoening
Brown adipose tissue, insulin resistance, non-shivering thermogenesis, skeletal muscle
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
1. Standard Uptake Values (SUV) of FDG in active BAT, as measured using FDG PET/CT scans (normal-fed period vs. prolonged fasting period);<br>
2. Energy expenditure, as measured using indirect calorimetry, during thermoneutral and mild cold conditions (normal-fed period vs. prolonged fasting period);<br>
3. Skeletal muscle mitochondrial uncoupling, as measured using high-resolution respirometry, in muscle biopsies (normal-fed period vs. prolonged fasting period);<br>
4. Ex vivo skeletal muscle insulin-stimulated glucose uptake, as a measure of insulin sensitivity (normal-fed period vs. prolonged fasting period).
Achtergrond van het onderzoek
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.
Doel van het onderzoek
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.
Onderzoeksopzet
Participation will take approximately 64 hours.
Onderzoeksproduct en/of interventie
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.
Publiek
M. Hanssen
Maastricht 6229 ER
The Netherlands
+31 (0)43 3884259
mjw.hanssen@maastrichtuniversity.nl/
Wetenschappelijk
M. Hanssen
Maastricht 6229 ER
The Netherlands
+31 (0)43 3884259
mjw.hanssen@maastrichtuniversity.nl/
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
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).
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
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.
Opzet
Deelname
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| Register | ID |
|---|---|
| NTR-new | NL3375 |
| NTR-old | NTR3523 |
| Ander register | METC MUMC / CCMO : 12-3-010 / NL39816.068.12; |
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