Ghrelin and LEAP-2: Rivals in Energy Metabolism

Liver-expressed antimicrobial peptide 2 (LEAP-2), the endogenous noncompetitive allosteric antagonist of the growth hormone secretagogue receptor 1a (GHSR1a), was recently identified as a key endocrine factor regulating systemic energy metabolism. This antagonist impairs the ability of ghrelin to activate GHSR1a and diminishes ghrelin-induced Ca2+ release in vitro. The physiological relevance of the molecular LEAP-2-GHSR1a interaction was subsequently demonstrated in vivo. LEAP-2 is therefore a promising therapeutic target in the treatment of obesity and other metabolic diseases. Here, we discuss not only the current understanding of LEAP-2 in metabolic regulation, but also the potential of this peptide in the treatment of obesity and other diseases that involve dysregulation of the ghrelin system.