Molecular variants of ghrelin

Ghrelin is the most powerful orexigenic hormone known. In healthy individuals, plasma ghrelin levels rise before scheduled meals and then fall to baseline levels, whereas in people with metabolic disorders, such as obesity and anorexia nervosa, baseline plasma ghrelin levels are generally altered. The proteolytic processing of a large number of peptide hormones has been described, and shown to give rise to shorter peptides, whose biological activities may differ from the full-length hormone. On the other hand, it is known that ghrelin is cleaved by plasma proteases and that the initial residues at the N-terminal end are essential for its binding to GHSR. Thus, we are investigating if the proteolysis of plasma ghrelin is an additional process that influences its plasma concentration and generates shorter ghrelin-derived forms with different biological activity.