Ghrelin and LEAP-2: Rivals in Energy Metabolism

Trends Pharmacol Sci. 2018 Aug;39(8):685-694. doi: 10.1016/j.tips.2018.06.004. Epub 2018 Jun 29.

Abstract

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.

Keywords: GH; GHSR1a; LEAP-2; food intake; ghrelin; metabolic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / agonists
  • Antimicrobial Cationic Peptides / antagonists & inhibitors
  • Antimicrobial Cationic Peptides / metabolism
  • Blood Proteins / agonists
  • Blood Proteins / antagonists & inhibitors
  • Blood Proteins / metabolism
  • Endocrine System / metabolism
  • Energy Metabolism
  • Ghrelin / metabolism*
  • Glucose / metabolism
  • Hepcidins / metabolism*
  • Humans
  • Neurosecretory Systems / metabolism
  • Obesity / drug therapy
  • Obesity / metabolism
  • Receptors, Ghrelin / agonists
  • Receptors, Ghrelin / antagonists & inhibitors
  • Receptors, Ghrelin / metabolism*

Substances

  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Ghrelin
  • Hepcidins
  • Receptors, Ghrelin
  • liver-expressed antimicrobial peptide 2, human
  • Glucose