The effects of intravenous TRH administration on brown adipose tissue activity in healthy, lean men.

Brown adipose tissue (BAT) is a well known major site of non-shivering
thermogenesis in most mammals. It was only recently found to be present and
active in human adults. Several studies have shown that BAT activity is
increased in adult humans during cold exposure. Animal experiments show that
heat production by BAT in response to cold is centrally regulated via
cold-sensitive TRH-neurons in hypothalamus and hindbrain, which in turn
activate sympathetic neurons in the spinal cord projecting to BAT. In animals,
TRH plays a major role in the central regulation of BAT. Hence, central and
systemic TRH administration causes a rise in BAT activity, an increase in body
temperature and sympathetic tone.
Data suggests that human BAT participates in the control of energy expenditure
and adiposity, making it an interesting potential new target for treatment of
obesity and diabetes. Whether TRH plays a role in BAT activation in response to
cold in humans, is unknown.
In this study, we aim to determine whether TRH administration stimulates BAT
activity and sympathetic tone in adult humans.

To investigate whether BAT tissue can be activated by intravenous
administration of TRH. Secondary objectives are to determine whether
intravenous TRH increases the degree of cardiovascular sympathetic stimulation
and the response of skin temperature, and whether there is a correlation
between the BAT-activity and these changes.

A double-blind, randomized, placebo-controlled cross-over study.

Intravenous TRH administration.

Subjects will be invited to the hospital twice with an interval of minimally 7
days. Subjects will be asked to refrain from exercise and to fast 6 hours prior
to study participation.
During the study, subjects will receive an intravenous cannula, through which
they receive infusions of 18F-FDG, TRH and saline, and from which 7 blood
samples will be collected. Placement of the intravenous cannula can be an
unpleasant experience. There is a small chance of developing phlebitis.
Subjects will be exposed to a mild cold (18C) for one hour.
Subjects will undergo dynamic PET-CT imaging, cardiovascular monitoring and
temperature monitoring. Side effects after intravenous TRH administration are
minimal, and may include nausea, flushing, urinary urgency and changes in blood
pressure. The total resulting dose from the whole-body 18F-FDG PET/CT
examinations is 7.2 mSv, which is less than 3 times the annual natural
background radiation exposure in the Netherlands. There are no further risks or
benefits associated with participation.