Unacylated ghrelin (UAG)

Unacylated ghrelin is the predominant circulating form of the peptide hormone ghrelin. Unlike its acylated counterpart, unacylated ghrelin does **not** bind or activate the canonical growth hormone secretagogue receptor type 1a (GHSR1a), but it exhibits distinct biological activities through alternative mechanisms. It has been shown to inhibit skeletal muscle atrophy and promote regeneration via GHSR1a-independent pathways involving PI3Kβ-, mTORC2-, and p38 MAPK signaling. In metabolic contexts, unacylated ghrelin improves insulin sensitivity, reduces oxidative stress and inflammation in skeletal muscle, prevents obesity-associated hyperglycemia and insulin resistance, and may stimulate autophagy for tissue protection. In oncology research models such as breast cancer cell lines grown in three-dimensional culture systems, unacylated ghrelin can suppress tumor cell proliferation by inducing cell cycle arrest and apoptosis—effects that are mediated by Gαi proteins affecting cAMP levels as well as modulation of MAPK pathway activity. Its roles are being explored for therapeutic potential against cachexia/muscle wasting syndromes, metabolic diseases like diabetes/obesity, cardiovascular conditions such as peripheral artery disease due to its antioxidant properties promoting tissue repair after ischemia/reperfusion injury—and possibly certain cancers due to anti-proliferative actions[2][3][6][9][10].

Other names

UnAGdes-acyl ghrelindesacyl-ghrelinnonacylated ghrelin

Does not bind or activate the classical growth hormone secretagogue receptor (GHSR1a), unlike acylated ghrelin[3][6]. Exerts effects via GHSR1a-independent pathways, including PI3Kβ-, mTORC2-, p38 MAPK signaling in muscle cells[6]. May act through Gαi protein-mediated reduction in cAMP levels in some cancer models[2].