Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight
Laurie L. Baggio, Daniel J. Drucker
Laurie L. Baggio, Daniel J. Drucker
Published September 9, 2014
Citation Information: J Clin Invest. 2014;124(10):4223-4226. https://doi.org/10.1172/JCI78371.
View: Text | PDF
Commentary

Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight

  • Text
  • PDF
Abstract

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.

Authors

Laurie L. Baggio, Daniel J. Drucker

×

Figure 1

Peripherally administered GLP-1R agonists reduce food intake and body weight through signaling mechanisms requiring functional GLP-1Rs in the ARC of the hypothalamus.

Options: View larger image (or click on image) Download as PowerPoint
Peripherally administered GLP-1R agonists reduce food intake and body we...
Several regions of the brain express GLP-1Rs, including the ARC, PVN, and subfornical organ (SFO), and signals from GLP-1 are transmitted through the vagus nerve or converge on the NTS and area postrema (AP). GLP-1 directly activates POMC/CART neurons and indirectly inhibits, via GABAergic transmission, the neuropeptide Y/agouti-related peptide (NPY/AgRP) neurons, which collectively results in signals that reduce food intake. Although GLP-1 generates signals that are transmitted through the vagus nerve or converge on the NTS or PVN of the hypothalamus (Hyp), these regions are not required to transduce an anorectic GLP-1R–dependent signal.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts