Activation of Brown Adipose Tissue in Old and Young Individuals

Brown adipose tissue (BAT) is known for its capacity to burn excess energy as
part of a process called non-shivering thermogenesis. Several studies have
shown that BAT activity is lower with increasing age, the exact explanation for
this is not known. Since BAT is principally activated by stimulation via the
sympathetic nervous system, the diminishing BAT activity with increasing age
may be a result of relatively low sympathetic stimulation of BAT.
In a previous study (METC 10/307, NL34861.018.10), we were able to
quantitatively measure and visualize the sympathetic stimulation of BAT using
I-123 Metaiodobenzylguanidine (MIBG) SPECT-CT scans. In this study we aim to
determine whether the sympathetic stimulation of BAT changes with increasing
age in individuals and if so, how this relates to the metabolic activity of BAT.

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

Primairy objective: To investigate whether the sympathetic stimulation of BAT,
as assessed with a MIBG SPECT-CT scan, differs between young and elderly
subjects.
Secondary Objectives:
1) 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 18-F fluorodeoxyglucose (FDG) PET-CT, differs between
young and elderly subjects.
2) To determine whether there is a difference in energy expenditure during
thermoneutral conditions and during mild cold exposure (in young and elderly
subjects).
3) To determine whether the difference in resting energy expenditure during
thermoneutral conditions and during mild cold exposure correlates with the
sympathetic stimulation of BAT as assessed with MIBG, and with metabolic BAT
activity as assessed with FDG (in young and elderly subjects).
4) To determine whether the difference insulin sensitivity correlates with the
sympathetic stimulation of BAT as assessed with a MIBG SPECT-CT scan, and with
metabolic BAT activity as assessed with FDG PET-CT (in young and elderly
subjects).

Observational design with invasive measurements

Included subjects will visit the AMC hospital on 3 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: Cold exposure, Intravenous administration of FDG, measurement of
resting energy expenditure, core body temperature, and an EMG, during cold and
FDG PET-CT scan.
Visit 3: 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 at thermoneutrality.

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.
The placement of the rectal thermometer can be an unpleasant experience.

There is no direct benefit for the volunteers. This research will provide
insight into the mechanism of brown fat activation, which may help us to
develop methods to combat obesity and diabetes.