The pharmacology and function of receptors for short-chain fatty acids

Bolognini, D., Tobin, A. B., Milligan, G. and Moss, C. E. (2016) The pharmacology and function of receptors for short-chain fatty acids. Molecular Pharmacology, 89(3), pp. 388-398. (doi:10.1124/mol.115.102301) (PMID:26719580)

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Abstract

Despite some blockbuster G protein–coupled receptor (GPCR) drugs, only a small fraction (∼15%) of the more than 390 nonodorant GPCRs have been successfully targeted by the pharmaceutical industry. One way that this issue might be addressed is via translation of recent deorphanization programs that have opened the prospect of extending the reach of new medicine design to novel receptor types with potential therapeutic value. Prominent among these receptors are those that respond to short-chain free fatty acids of carbon chain length 2–6. These receptors, FFA2 (GPR43) and FFA3 (GPR41), are each predominantly activated by the short-chain fatty acids acetate, propionate, and butyrate, ligands that originate largely as fermentation by-products of anaerobic bacteria in the gut. However, the presence of FFA2 and FFA3 on pancreatic β-cells, FFA3 on neurons, and FFA2 on leukocytes and adipocytes means that the biologic role of these receptors likely extends beyond the widely accepted role of regulating peptide hormone release from enteroendocrine cells in the gut. Here, we review the physiologic roles of FFA2 and FFA3, the recent development and use of receptor-selective pharmacological tool compounds and genetic models available to study these receptors, and present evidence of the potential therapeutic value of targeting this emerging receptor pair.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bolognini, Dr Daniele and Milligan, Professor Graeme
Authors: Bolognini, D., Tobin, A. B., Milligan, G., and Moss, C. E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Molecular Pharmacology
Publisher:American Society for Pharmacology and Experimental Therapeutics
ISSN:1521-0111
ISSN (Online):1521-0111
Published Online:30 December 2015
Copyright Holders:Copyright © 2016 American Society for Pharmacology and Experimental Therapeutics
First Published:First published in Molecular Pharmacology 89(3):388-398
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
618921GPR120: a G protein-coupled receptor with the potential to regulate insulin secretion and inflammationGraeme MilliganBiotechnology and Biological Sciences Research Council (BBSRC)BB/K019864/1RI MOLECULAR CELL & SYSTEMS BIOLOGY