Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight
Open accessAbstract
The peptide hormone glucagon-like peptide-1 (GLP-1) enhances glucose-induced insulin secretion and inhibits both gastric emptying and glucagon secretion. GLP-1 receptor (GLP-1R) agonists control glycemia via glucose-dependent mechanisms of action and promote weight loss in obese and diabetic individuals. Nevertheless, the mechanisms and cellular targets transducing the weight loss effects remain unclear. Two recent studies in the JCI provide insight into the neurons responsible for this effect. Sisley et al. reveal that GLP-1R agonist-induced weight loss requires GLP-1Rs in the CNS, while Secher et al. reveal that a small peptide GLP-1R agonist penetrates the brain and activates a subset of GLP-1R-expressing neurons in the arcuate nucleus to produce weight loss. Together, these two studies elucidate pathways that inform strategies coupling GLP-1R signaling to control of body weight in patients with diabetes or obesity.
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GLP-1s activate several brain regions responsible for weight regulation, appetite, and nausea.
“GLP‐1s activate several brain regions responsible for weight regulation, appetite, and nausea [51].”
From Nutritional priorities to support <scp>GLP</scp> ‐1 therapy for obesity: A joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society (2025) · cites this paper as [51]
The figure caption in Conclusions and future directions (page unavailable) describes GLP-1 signaling in several brain regions and its effects on food intake and body weight. Complex GLP-1-dependent pathways and effects (page unavailable) reports nausea as a side effect of GLP-1R agonists, but does not establish that activation of particular brain regions causes it. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGLP-1's action in the brain reduces appetite and may influence energy expenditure.
“And GLP-1’s action in the brain reduces appetite and may influence energy expenditure.176,210,211”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [211]
Chronic activation of central GLP-1 receptors can cause weight loss by reducing food intake through increased satiety.
“Chronic activation of central GLP-1Rs can lead to body weight loss 15 by reducing food intake 16 through promotion of satiety 14”
From Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists (2024) · cites this paper as [15]
GLP-1s activate several brain regions responsible for weight regulation, appetite, and nausea.
“GLP-1s activate several brain regions responsible for weight regulation, appetite, and nausea [51].”
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References 20 · Cited by 245
Research works printed but not linked: 2
- [3]3. Meeran K, et al. Repeated intracerebroven- tricular administration of glucagon-like peptide-1-(7-36) amide or exendin-(9-39) alters body weight in the rat. Endocrinology. 1999;140(1):244-250.
- [18]18. Sadry SA, Drucker DJ. Emerging combina- J Clin Invest. 2014;124(10):4473-4488.
- Authors
- Baggio, L. L., & Drucker, D. J.
- Corresponding author
- Drucker, Daniel J.
- ORCID
- Drucker, Daniel J.
- Venue
- Journal of Clinical Investigation
- Published
- 2014-09-09
- Volume
- 124
- Issue
- 10
- Pages
- 4223-4226
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC4191040
- OpenAlex
- W1982999222
- Cited by
- 245
- References
- 20
- Citations by year
- 2026: 39 · 2025: 46 · 2024: 36 · 2023: 22 · 2022: 15 · 2021: 12 · 2020: 13 · 2019: 9 · 2018: 9 · 2017: 17 · 2016: 14 · 2015: 13
- FWCI
- 7.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- Banting and Best Diabetes Centre, University of Toronto
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- GLP-1 receptor, GLP-1 receptor agonists, brain, dietary intake, body weight regulation, arcuate nucleus, weight loss, obesity, diabetes mellitus, insulin secretion, gastric emptying, glucagon secretion
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