Reviews in Endocrine and Metabolic Disorders

, Volume 12, Issue 3, pp 173–186

The ghrelin/GOAT/GHS-R system and energy metabolism

Authors

  • Chung Thong Lim
    • Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and DentistryQueen Mary University of London
  • Blerina Kola
    • Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and DentistryQueen Mary University of London
    • Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and DentistryQueen Mary University of London
Article

DOI: 10.1007/s11154-011-9169-1

Cite this article as:
Lim, C.T., Kola, B. & Korbonits, M. Rev Endocr Metab Disord (2011) 12: 173. doi:10.1007/s11154-011-9169-1

Abstract

Ghrelin is a brain-gut peptide that was discovered through reverse pharmacology and was first isolated from extracts of porcine stomach. Ghrelin binds to growth hormone secretagogue receptor (GHS-R) and is acylated on its serine 3 residue by ghrelin O-acyltransferase (GOAT). Several important biological functions of ghrelin have been identified, which include its growth hormone-releasing and appetite-inducing effects. Ghrelin exerts its central orexigenic effect mainly by acting on the hypothalamic arcuate nucleus via the activation of the GHS-R. Peripherally ghrelin has multiple metabolic effects which include promoting gluconeogenesis and fat deposition. These effects together with the increased food intake lead to an overall body weight gain. AMP-activated protein kinase, which is a key enzyme in energy homeostasis, has been shown to mediate the central and peripheral metabolic effects of ghrelin. The hypothalamic fatty acid pathway, hypothalamic mitochondrial respiration and uncoupling protein 2 have all been shown to act as the downstream targets of AMPK in mediating the orexigenic effects of ghrelin. Abnormal levels of ghrelin are associated with several metabolic conditions such as obesity, type 2 diabetes, Prader-Willi syndrome and anorexia nervosa. The ghrelin/GOAT/GHS-R system is now recognised as a potential target for the development of anti-obesity treatment.

Keywords

GhrelinGOATGHS-RAppetiteAMPKObesity

Copyright information

© Springer Science+Business Media, LLC 2011