Trial Information

The Role of GLP-1 in Satiety Perception in Humans

Many times each day, we see food or representations of food and evaluate whether or not the
food looks good to us. If it does, we then balance external factors, such as the social
situation or time of day, against internal signals about our hunger state in order to decide
what and when to eat. However, recent functional magnetic resonance imaging (fMRI) studies
suggest that internal signals, such as hormones regulating appetite and satiety, govern our
food intake in part by acting on neural circuits to affect whether a given food appears
appetizing at that moment. In addition, photographs of food perceived to be "fattening"
activate brain regions involved in appetite and reward processing, including the
hypothalamus, nucleus accumbens, and orbital frontal cortex. This activity is potently
reduced by food intake, suggesting that it reflects underlying brain mechanisms involved in
satiety. We now propose to study the mechanism of these changes in brain activity by asking
if they are directly related to the action of glucagon-like peptide-1 (GLP-1), a satiety
signal. GLP-1 is released by cells in the gut in response to nutrients, suppressing food
intake, and its actions can be blocked by a GLP-1 receptor antagonist, exendin-[9-39]. In 2
randomized, controlled, crossover studies, we will assess whether exendin-[9-39] infusions
reverse GLP-1-mediated effects on food intake and on brain response to visual food cues. Our
scientific aims are to 1) observe the effect of exendin (9-39) on blocking GLP-1-mediated
satiety in humans and assess its effect on food intake in humans for the first time (to our
knowledge) and 2) to test whether endogenous GLP-1 signaling is required for the effect of a
meal to reduce brain response to visual food cues in humans. We hypothesize that
exendin-[9-39] will diminish the effect of a meal in suppressing subsequent food intake and
in reducing activation to visual food cues in reward pathways. Determining the extent to
which the experience of satiety arises from a decrease in the reward value of food is
fundamentally important to understanding human feeding behavior. In addition, this promising
line of research is directly relevant to some of the most pressing public health issues of
our time: obesity and overnutrition. We hope that investigating mechanisms affecting our
perception of satiety at the most basic level will eventually result in novel behavioral or
pharmacologic strategies for obesity prevention and treatment.