Prouroguanylin is a gastrointestinal paracrine signal and prohormone that is secreted after nutrient ingestion. In this issue of the JCI, Valentino et al. show that prouroguanylin is converted to uroguanylin in the CNS, which can activate guanylyl cyclase 2C (GUCY2C) receptors in the brain to reduce food intake in mice. This 16–amino acid residue peptide is a novel component of the gut-brain axis that represents a new and unique opportunity to manipulate gut-brain signaling for therapeutic intervention in obesity.
