The effect of cold acclimation on human brown adipose tissue and skeletal muscle uncoupling

Upon mild cold exposure people can increase their energy expenditure. This is
called non-shivering thermogenesis (NST). Moreover, during prolonged cold
exposure NST can increase, this is called adaptive thermogenesis (AT). This
metabolic reaction is subject to high inter-individual variability. These
differences might be explained by the amount of active brown adipose tissue
(BAT). Furthermore, a negative correlation between BAT activity and BMI was
found and obese people show an impaired cold-induced thermogenesis. In rodents,
BAT and the skeletal muscle are mainly responsible for NST, and upon chronic
cold exposure recruitment of BAT takes place. Recently, we showed that severe
weight loss in obese subjects causes BAT recruitment, and BAT activity
correlates with NST. Moreover, white fat cells can be converted into brown-like
cells, called BRITE cell recruitment. Chronic cold exposure in healthy men
showed a decrease in shivering with remaining elevated energy expenditure; this
indicates that humans are also capable to increase NST.

It is hypothesized that upon chronic cold exposure in healthy, lean adults BAT
and BRITE recruitment will take place. Furthermore, skeletal muscle
mitochondrial uncoupling and adaptive thermogenesis will increase.

The primary objectives of this study are: (1) To establish the role of brown
adipose tissue in cold-induced thermogenesis before and after a cold
acclimation period; (2) to study the involvement of skeletal muscle
mitochondrial uncoupling in cold-induced thermogenesis and (3) to study the
effect of chronic cold exposure on the white adipose tissue depot.

The volunteers will undergo two PET/CT-scans, in which cold-induced BAT
activity will be measured before and after a cold acclimation period of 10
days. To investigate the role of the skeletal muscle mitochondrial uncoupling
and BRITE cell recruitment a muscle and fat biopsy sample will be taken prior
to the acclimation period and afterwards. Finally, body composition will be
determined with a DXA-scan, and skin perfusion and relevant body temperatures
will be measured as well.

Cold exposure. For 10 consecutive days the subjects will be exposed to cold (12
C).
To easily get used to this, exposure will be 2hours at the 1st day, 4hours at
the 2nd day and day 3-10 6hours/day.

The risks of this study are low.
The total effective dose is low and will not give any risk to the subjects
The total absorbed radiation dose from two FDG-PET/CT-scans after
administration of two times 74 MBq of 18F-FDG is 6.4 mSv.
This is about three times the background radiation in the Netherlands and is
below the criteria as stated in ICRP-60, <10 mSv.