The Role of GLP-1 in Satiety Perception in Humans
| Status: | Completed |
|---|---|
| Conditions: | Food Studies, Obesity Weight Loss |
| Therapuetic Areas: | Endocrinology, Pharmacology / Toxicology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 11/18/2012 |
| Start Date: | July 2010 |
| End Date: | July 2011 |
| Contact: | Vidhi Tyagi |
| Email: | vtyagi@u.washington.edu |
| Phone: | 206-744-1825 |
Scientists have discovered a number of hormones that control our feelings of hunger and
fullness. One particular hormone, called GLP-1, has been associated with feelings of hunger
and fullness. The overall purpose of this study is to look more closely at how GLP-1
changes these feelings and to observe how these hormones affect the brain's function. To do
this, volunteers will be asked to come to the clinic for a screening visit, and 2 study
visits. This is an outpatient study with a screening visit which will last about an hour
and the two subsequent study visits for about 3 hours each. During the study, patients will
receive a drug that blocks the effect of a hormone made in the gut. We will take a series
of blood samples to measure hormones and use functional magnetic resonance imaging (MRI) to
take pictures of the brain. Understanding the action of these hormones in the brain may
eventually lead to new ways to help people avoid obesity or lose weight.
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.
Inclusion Criteria:
1. Male or female between 18-29 years of age
2. BMI between 18.5-24.9 kg/m2
3. Written informed consent obtained from subject and ability for subject to comply with
the requirements of the study.
Exclusion Criteria:
1. Chronic health conditions, including diabetes and kidney disease.
2. Current dieting for weight loss or restrained eating
3. History of obesity, eating disorders, or weight loss surgery
4. Random blood glucose >140
5. Pregnancy or use of oral contraceptives
6. Current smoker
7. Recreational drug use or alcohol use of > 1 drink per day for females, > 2 per day
for males
8. Food allergy or intolerance to study foods.
9. Medications known to alter appetite (e.g., amphetamines, atypical antipsychotics) or
gastric emptying (e.g., metoclopromide)
10. Contraindications to MRI, such as implanted metal or claustrophobia.
11. Presence of a condition or abnormality that in the opinion of the Investigator would
compromise the safety of the patient or the quality of the data.
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