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 October 1, 2014; First published September 9, 2014
Citation Information: J Clin Invest. 2014;124(10):4223-4226. https://doi.org/10.1172/JCI78371.
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Commentary

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

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

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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.

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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.