Uroguanylin: how the gut got another satiety hormone

Abstract

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.

Figure 1. Prouroguanylin is a prohormone that is secreted by the GI tract.

It has been shown to be cleaved in the lumen of the GI tract to the active hormone, uroguanylin, that can activate GUCY2C receptors to alter fluid absorption. In this issue of the JCI, Valentino et al. (5) show that prouroguanylin levels in the blood are increased after meals. It can then be cleaved to uroguanylin in the CNS to interact with GUCY2C receptors in the hypothalamus to decrease food intake and thereby act as a satiety factor from gut to brain.