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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.

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