Effects of FASTING duration on cerebral serotonin and dopamine transporter availability in lean and obese subjects

Feeding behaviour is regulated by a complex interplay of the homeostatic and
hedonic systems, and is influenced by peripheral inputs. The neurotransmitters
serotonin and dopamine have major roles in the cerebral regulation of feeding
behaviour by mediating anorexigenic and orexigenic signals, respectively.
Cerebral availability of the serotonin and dopamine transporters (SERT and DAT)
is representative of the cerebral serotonin and dopamine system.
In obesity, control of food intake is disturbed, resulting in overconsumption
of high-calorie nutrients. Therefore, the role of the central nervous system,
and SERT and DAT in particular, in the current obesity epidemic is an active
interest of ongoing research worldwide.
Fasting influences neural signals and hormones that provide cognitive and
peripheral input to the central regulation of food intake. Studying the effects
of fasting on the brain areas involved in overeating/obesity, as well as
differences in the response to fasting between lean and obese individuals, may
unravel novel therapeutic targets for (the prevention of) obesity.
In addition, since it is currently unknown how fasting affects central SERT and
DAT, interpretation of previous studies that investigate effects of lifestyle,
diet and/or metabolic challenges on cerebral serotonin and dopamine in humans
is complicated. These studies vary in fasting duration prior to the measurement
of cerebral SERT and DAT availability, possibly confounding the results.

To investigate the effect of fasting duration on cerebral SERT and DAT
availability.

Randomized controlled crossover study

Subjects will visit the AMC on two occasions. Prior to these visits, subjects
will consume a standardized eucaloric diet for three days. After 12 or 24 hours
of fasting, central SERT and DAT availability will be assessed by SPECT using
an intravenous infusion of the radioligand [123I]FP-CIT. [123I]FP-CIT has a
European (CPMP) registration, and it has been shown that it has no serious side
effects. As the dose equivalent per [123I]FP-CIT injection amounts to 2.4 mSv
(100MBq), the total dose equivalent of the subjects will be 4.8 mSv. Venous
blood samples will be drawn on both visits. Risks associated by participation
(thyroid uptake of radioligand, exposure to radiation) will be kept to a
minimum by providing subjects with potassium iodide tablets to reduce uptake of
the radioligand in the thyroid, and keeping the total dose equivalent far below
the currently recommended maximum dose equivalent for research participants
(i.e., 15.3 mSv (222 MBq), WHO category IIb, men >50 years).