Des-Acyl Ghrelin
Metabolic / Body CompositionAlso known as: Unacylated Ghrelin, UAG, Des-Octanoyl Ghrelin
Mechanism
Des-acyl ghrelin is the unacylated (non-octanoylated) form of ghrelin that lacks the fatty acid modification needed to activate the classical ghrelin receptor (GHS-R1a). Despite this, it is the predominant form of ghrelin in circulation (80-90%) and has its own biological activities — including improvements in insulin sensitivity, glucose metabolism, and cardioprotection — often opposing the appetite-stimulating effects of acylated ghrelin.
Technical detail
Des-acyl ghrelin is the 28-amino-acid ghrelin peptide lacking the Ser3-octanoylation required for GHS-R1a binding and activation. It constitutes 80-90% of total circulating ghrelin. Despite inability to activate GHS-R1a, it exerts biological effects through putative unidentified receptor(s) or through heterodimerization-mediated modulation of GHS-R1a signaling. It improves insulin sensitivity and glucose tolerance via enhanced pancreatic beta-cell function, demonstrates anti-apoptotic effects in cardiomyocytes, and antagonizes acyl-ghrelin's orexigenic (appetite-stimulating) effects. AZP-531 (livoletide), a des-acyl ghrelin analog, entered Phase 2 trials for Prader-Willi syndrome.