abstract |
Ghrelin is a peptide hormone that binds to its receptor, growth hormone secretion promoting factor receptor 1a (GHS-R1a, ghrelin receptor), and promotes adiposity and obesity in mammals. Ghrelin and its receptor are targets for therapeutic interventions to treat obesity-related diseases and cancer. A soluble decoy GHS-R1a receptor is developed that binds ghrelin in the periphery and prevents ghrelin from binding to GHS-R1 on cells, thereby antagonizing ghrelin and treating obesity-related conditions and cancer. GHS-R1a is a transmembrane protein comprising an N-terminal extracellular domain (Nt), a seven transmembrane region, and three extracellular loops (EC1, EC2, and EC3). Nt, EC1 and EC2 are not linked together, there is no transmembrane region, and they are fused with immunoglobulin-derived Fc to form a decoy GHS-R1a fusion protein GHSR-Fc. GHSR-Fc suppresses adiposity and weight gain in mice on a high fat diet (HFD), whereas Nt and EC have no significant effect on their own. |