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Trends Pharmacol Sci. 2008 Aug;29(8):398-401. doi: 10.1016/j.tips.2008.06.003. Epub 2008 Jul 6.

Introducing GOAT: a target for obesity and anti-diabetic drugs?

Author information

1
Neuroendocrine Interactions in Rheumatology and Inflammatory Disease, University of Santiago Clinical Hospital,15706 Santiago de Compostela, Spain. oreste.gualillo@sergas.es

Abstract

The acyltransferase that catalyzes ghrelin octanoylation has recently been identified as ghrelin O-acyltransferase (GOAT). GOAT belongs to a family of membrane-bound O-acyltransferases (MBOATs). GOAT covalently links a medium fatty-acid chain, typically octanoate, to the hydroxyl group of the third serine of ghrelin, a potent orexigenic peptide characterized by this unique post-translational modification. The discovery of GOAT raises important questions and reveals several therapeutical possibilities. Indeed, drugs that inhibit GOAT might be able to prevent diet-induced obesity and might be an effective therapy for type-2 diabetes, increasing insulin secretion and enhancing peripheral insulin sensitivity. Furthermore, research on GOAT is providing new insights into the pathophysiology of energy homeostasis and might lead to the identification of further therapeutic targets. Here, we review what is currently known about the regulatory role of GOAT and discuss the potential of this novel approach for treating obesity and type-2 diabetes.

PMID:
18606462
DOI:
10.1016/j.tips.2008.06.003
[Indexed for MEDLINE]

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