Brain reward-system activation in response to anticipation and consumption of palatable food is altered by glucagon-like peptide-1 receptor activation in humans
Open accessAbstract
Aim: To test the hypothesis that food intake reduction after glucagon‐like peptide‐1 ( GLP ‐1) receptor activation is mediated through brain areas regulating anticipatory and consummatory food reward. Methods: As part of a larger study, we determined the effects of GLP ‐1 receptor activation on brain responses to anticipation and receipt of chocolate milk versus a tasteless solution, using functional MRI ( fMRI ). Obese subjects with type 2 diabetes, and obese and lean subjects with normoglycaemia (n = 48) underwent three fMRI sessions at separate visits with intravenous infusion of the GLP ‐1 receptor agonist exenatide, exenatide with prior GLP ‐1 receptor blockade by exendin‐9‐39 or placebo, during somatostatin pituitary‐pancreatic clamps. Results: Body mass index negatively correlated with brain responses to receipt of chocolate milk and positively correlated with anticipation of receipt of chocolate milk in brain areas regulating reward, appetite and motivation. Exenatide increased brain responses to receipt of chocolate milk and decreased anticipation of receipt of chocolate milk compared with placebo, paralleled by reductions in food intake. Exendin‐9‐39 largely prevented these effects. Conclusions: Our findings show that GLP ‐1 receptor activation decreases anticipatory food reward, which may reduce cravings for food and increases consummatory food reward, which may prevent overeating.
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In humans, the administration of GLP-1RAs reduces appetite, decreases energy intake, and increases satiety.
“In humans, the administration of GLP-1RAs reduces appetite, decreases energy intake, and increases satiety.”
From GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review (2024) · cites this paper as [12]
The ‘Effects of GLP-1 Receptor Activation on ad libitum Food Intake and Hunger Scores’ section reports reduced caloric intake during exenatide infusion in all three human groups. It also reports no significant differences in appetite or fullness scores, so this study does not establish the claimed appetite reduction or increased satiety. (LLM, conf=0.89)
Experimental — accuracy not yet measuredFunctional magnetic resonance imaging (MRI) shows that GLP-1 R activation decreases anticipatory food reward.
“Functional magnetic resonance imaging (MRI) shows that GLP-1 R activation decreases anticipatory food reward (the anticipated pleasure of eating certain meals).12”
From GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review (2024) · cites this paper as [12]
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- Authors
- van Bloemendaal, L., Veltman, D. J., ten Kulve, J. S., Groot, P. F. C., Ruhé, H. G., Barkhof, F., Sloan, J. H., Diamant, M., & Ijzerman, R. G.
- Affiliations
- Department of Internal Medicine Diabetes Centre, VU University Medical Centre Amsterdam The Netherlands
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Amsterdam UMC Location University of Amsterdam (NL)
- University Medical Center Groningen (NL)
- Eli Lilly (United States) (US)
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2015-07-22
- Volume
- 17
- Issue
- 9
- Pages
- 878-886
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2153706938
- Cited by
- 151
- References
- 48
- Citations by year
- 2026: 22 · 2025: 15 · 2024: 22 · 2023: 12 · 2022: 9 · 2021: 16 · 2020: 14 · 2019: 7 · 2018: 12 · 2017: 8 · 2016: 12 · 2015: 2
- FWCI
- 6.28
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Eli Lilly and Company
- Bristol-Myers Squibb
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- GLP-1 receptor, exenatide, exendin-9-39, food reward, palatable food, chocolate milk, obesity, type 2 diabetes, hypophagia, appetite, brain activation
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Exenatide, Adult, Aged, Animals, Appetite, Brain, Cacao, Diabetes Mellitus, Type 2, Feeding Behavior, Female, Humans, Hypoglycemic Agents, Magnetic Resonance Imaging, Male, Middle Aged, Milk, Motivation, Obesity, Peptide Fragments, Peptides, Reward, Venoms, Anticipation, Psychological
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