Ghrelin and the brain-gut axis as a pharmacological target for appetite control

Seim, Inge, El-Salhy, Magdy, Hausken, Trygve, Gundersen, Doris, & Chopin, Lisa (2012) Ghrelin and the brain-gut axis as a pharmacological target for appetite control. Current Pharmaceutical Design, 18(6), pp. 768-775.

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Abstract

Appetite regulation is highly complex and involves a large number of orexigenic and anorexigenic peptide hormones. These are small, processed, secreted peptides derived from larger prepropeptide precursors. These peptides are important targets for the development of therapeutics for obesity, a global health epidemic. As a case study, we consider the ghrelin axis. The ghrelin axis is likely to be a particularly useful drug target, as it also plays a role in energy homeostasis, adipogenesis, insulin regulation and reward associated with food intake. Ghrelin is the only known circulating gut orexigenic peptide hormone. As it appears to play a role in diet-induced obesity, blocking the action of ghrelin is likely to be effective for treating and preventing obesity. The ghrelin peptide has been targeted using a number of approaches, with ghrelin mirror-image oligonucleotides (Spiegelmers) and immunotherapy showing some promise. The ghrelin receptor, the growth hormone secretagogue receptor, may also provide a useful target and a number of antagonists and inverse agonists have been developed. A particularly promising new target is the enzyme which octanoylates ghrelin, ghrelin O-acyltransferase (GOAT), and drugs that inhibit GOAT are likely to circumvent pharmacological issues associated with approaches that directly target ghrelin or its receptor.

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13 citations in Web of Science®

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ID Code: 69818
Item Type: Journal Article
Refereed: Yes
Keywords: Appetite, peptide hormone, ghrelin, GHSR, GOAT, epidemic, oligonucleotides, immunotherapy, Spiegelmers, cryptide
DOI: 10.2174/138161212799277806
ISSN: 1381-6128
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 03 Apr 2014 23:34
Last Modified: 11 Apr 2014 06:31

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