ArticleThe Journal of clinical investigation2014
The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 514 papers, 7 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
514 citing papers in PubMed, 7 syntheses or guidelines pooled it, 895 citations in OpenAlex.
- Comparing GLP-1 agonists versus other weight loss interventions on risk of atrial fibrillation recurrence after catheter ablation: a meta-analysis.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2026Pooled it
- Mapping GLP-1 receptor agonist research across the MASLD-MASH-HCC continuum: a bibliometric and translational analysis.Frontiers in medicine · 2026Pooled it
- Effects of glucagon-like peptide 1 receptor agonists on testicular dysfunction: A systematic review and meta-analysis.Andrology · 2025Pooled it
- Pooled it
- Depressive symptoms at short-, medium-, and long-term follow-up after bariatric surgical procedures: A systematic review and meta-analysis.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Pooled it
- Efficacy and Safety of GLP- 1 Receptor Agonists in the Management of Weight Recurrence or Suboptimal Clinical Response after Undergoing Metabolic Bariatric Surgeries: A Meta-Analysis.Obesity surgery · 2025Pooled it
- Current Insights, Advantages and Challenges of Small Molecule Glucagon-like Peptide 1 Receptor Agonists: A Scoping Review.Journal of Brown hospital medicine · 2025Pooled it
- Limited Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Appetite and Body Weight: Evidence From Clinical and Rodent Studies.Journal of Korean medical science · 2026Trial
- Effect of Efsubaglutide Alfa on the Pharmacokinetics of Metformin and Digoxin in Healthy Participants.Clinical pharmacokinetics · 2025Trial
- Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights.Nature metabolism · 2025Trial
- Glucagon-Like Peptide-1 Signaling in Learning and Memory: Evidence, Mechanisms, and Therapeutic Implications.Biological psychiatry · 2026Review
- Lipid sensing and brain hormone receptors in food intake and glucose regulation.Nature reviews. Endocrinology · 2026Review
- Effect of emerging antiobesity and antidiabetic drugs on atherosclerosis.Internal and emergency medicine · 2026Review
- Microbiota-Gut-Brain Axis Mechanisms in Cognitive Impairment Associated with Central Obesity.Current obesity reports · 2026Review
- Micronutrient risk with GLP-1 receptor and dual incretin agonists in obesity: Mechanistic pathways, clinical signals, and a monitoring framework.Obesity pillars · 2026Review
- Metabolic state determines the brain and direct islet effects of liraglutide on enhanced insulin secretion.Diabetologia · 2026Article
- Thermal challenge and food intake: Mutual regulatory mechanisms.Neural regeneration research · 2026Article
- Article
- GLP-1 and dual GIP/GLP-1 receptor agonists' psychopharmacology and putative neuropsychiatric associated effects: a Bradford Hill-informed, systematic, evaluation.Current psychiatry reports · 2026Review
- Semaglutide Alleviates LPS-Induced Cognitive Disorder via O-GlcNAcylation of AKT-mTOR Signaling Pathway Components.Neuromolecular medicine · 2026Article
454 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liraglutide is a glucagon-like peptide-1 (GLP-1) analog marketed for the treatment of type 2 diabetes. Besides lowering blood glucose, liraglutide also reduces body weight. It is not fully understood how liraglutide induces weight loss or to what degree liraglutide acts directly in the brain. Here, we determined that liraglutide does not activate GLP-1-producing neurons in the hindbrain, and liraglutide-dependent body weight reduction in rats was independent of GLP-1 receptors (GLP-1Rs) in the vagus nerve, area postrema, and paraventricular nucleus. Peripheral injection of fluorescently labeled liraglutide in mice revealed the presence of the drug in the circumventricular organs. Moreover, labeled liraglutide bound neurons within the arcuate nucleus (ARC) and other discrete sites in the hypothalamus. GLP-1R was necessary for liraglutide uptake in the brain, as liraglutide binding was not seen in Glp1r(-/-) mice. In the ARC, liraglutide was internalized in neurons expressing proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). Electrophysiological measurements of murine brain slices revealed that GLP-1 directly stimulates POMC/CART neurons and indirectly inhibits neurotransmission in neurons expressing neuropeptide Y (NPY) and agouti-related peptide (AgRP) via GABA-dependent signaling. Collectively, our findings indicate that the GLP-1R on POMC/CART-expressing ARC neurons likely mediates liraglutide-induced weight loss.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.