Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y.
AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown.
Scientists show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. They also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype.
Moreover, authors show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons.
The data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity.