Activation of brown adipose tissue in lean and obese men

Brown adipose tissue (BAT) has recently been identified as a possible mean to
significantly influence energy expenditure and glucose metabolism. Several
studies have shown that brown adipose tissue activity is much lower in obese
individuals when compared to their lean peers. The exact explanation for this
is not understood. As stimulation by the sympathetic nervous system is a
principal driving force for BAT activation in humans, the relatively low BAT
activity in obese individuals may be the result of a relatively low sympathetic
stimulation of BAT. In a previous study, we were able to quantitatively measure
and visualize the sympathetic stimulation of BAT using MIBG SPECT-CT scans. In
this study we aim to determine whether the sympathetic stimulation of BAT
differs between lean and obese individuals and if so, how this affects the
metabolic activity of BAT. Furthermore, we want to investigate the relation
between the sympathetic stimulation and metabolic activity of BAT with energy
expenditure in these individuals.

This research will provide insight into the mechanism of brown fat, which may
help us to develop methods to combat obesity and diabetes.

Main objective
To investigate whether the sympathetic stimulation of BAT, as assessed with a
MIBG SPECT-CT scan, differs between lean and obese individuals.



Secondary Objectives:

To investigate whether the slope of the correlation between sympathetic
stimulation of BAT as assessed with a MIBG SPECT-CT scan, and BAT activity
itself as assessed with FDG PET-CT, differs between lean and obese individuals.

To determine whether the difference in resting energy expenditure during
thermoneutral conditions and during mild cold exposure (i.e when BAT is active)
correlates with the sympathetic stimulation of BAT as assessed with MIBG, and
with metabolic BAT activity as assessed with FDG (both in lean and obese
individuals).

Observational desigh with invisive measurements

Included subjects will visit the AMC hospital on 4 occasions.
Visit 1: Informed consent, medical history, vital signs, laboratory
measurements, oral glucose tolerance test, electrocardiogram (ECG). Total blood
drawn: 67.5 ml.
Visit 2: 2 hours of cold-exposure, intravenous administration of FDG,
measurement of resting energy expenditure and FDG PET-CT
Visit 3: 2 hours of cold-exposure, intravenous administration of MIBG
Visit 4 (24 hours after visit 3): MIBG SPECT-CT scan (no new infusion of MIBG)
and measure of resting energy expenditure.

The resulting dose from the radioactive tracers + the scans is 9.6 mSv. The
placement of an intravenous canula can be an unpleasant experience and there is
a small chance of developing flebitis at the site of the intravenous canula.


There is no direct benefit for the volunteers. This study will provide new
insights into the activation of BAT. BAT activity has recently been identified
as a possible mean to significantly influence glucose metabolism and weight
status. However, knowledge on the exact mechanisms that influence BAT activity
is scarce. The findings of this study may help us to develop future methods to
combat obesity and diabetes.