Effects of FASTING the brain

Rationale: 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 rewarding signals, respectively. Extracellular levels of serotonin and dopamine are regulated by serotonin and dopamine transporters (SERT and DAT) respectively and they can be visualized using SPECT.

In obesity, control of food intake is disturbed, resulting in overconsumption of high-calorie nutrients. Therefore, the role of the central nervous system, and serotonin and dopamine in particular, in the current obesity epidemic is an active interest of ongoing research worldwide.
Fasting influences neural signals and hormones that provide input to the central regulation of food intake. Studying the effects of fasting on 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 troublesome because these studies vary in fasting duration prior to the measurement of cerebral SERT and DAT availability.

We hypothesize that 1) fasting duration may affect the central serotonin and dopamine systems, either centrally or indirectly through effects on peripheral input to the central nervous system, and 2) the effect of fasting may be changed in obesity.

2 SPECT scan study days: one preceded by 12 hours of fasting, the other by 24 hours of fasting

Fasting intervention: participants will undergo [123I]FP-CIT SPECT scans on two study days, prior to one study day participants will fast for 12 hours, prior to the other study day participants will fast for 24 hours.

Diet intervention: prior to each fasting intervention, participants will consume an eucaloric diet for 72 hours. Eucaloric enery requirements are based on resting energy expenditure measured with indirect calorimetry.