Chemogenetic approaches to explore the functions of Free Fatty Acid Receptor 2

Milligan, G. , Barki, N. and Tobin, A. (2021) Chemogenetic approaches to explore the functions of Free Fatty Acid Receptor 2. Trends in Pharmacological Sciences, 42(3), pp. 191-202. (doi: 10.1016/j.tips.2020.12.003) (PMID:33495026)

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Abstract

Short-chain fatty acids are generated in large amounts by the intestinal microbiota. They activate both the closely related G protein-coupled receptors free fatty acid receptor 2 (FFA2) and free fatty acid receptor 3 (FFA3) that are considered therapeutic targets in diseases of immuno-metabolism. Limited and species-selective small-molecule pharmacology has restricted our understanding of the distinct roles of these receptors. Replacement of mouse FFA2 with a designer receptor exclusively activated by designer drug form of human FFA2 (hFFA2-DREADD) has allowed definition of specific roles of FFA2 in pharmacological and physiological studies conducted both ex vivo and in vivo, whilst overlay of murine disease models offers opportunities for therapeutic validation prior to human studies. Similar approaches can potentially be used to define roles of other poorly characterised receptors.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Barki, Ms Natasja and Milligan, Professor Graeme and Tobin, Andrew
Authors: Milligan, G., Barki, N., and Tobin, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Trends in Pharmacological Sciences
Publisher:Elsevier (Cell Press)
ISSN:0165-6147
ISSN (Online):1873-3735
Published Online:22 January 2021
Copyright Holders:Copyright © 2020 Elsevier
First Published:First published in Trends in Pharmacological Sciences 42(3): 191-202
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
302989Defining physiological and pathophysiological roles of the Free Fatty Acid Receptor 2 by analysis of novel transgenic mouse modelsGraeme MilliganBiotechnology and Biological Sciences Research Council (BBSRC)BB/S000453/1Institute of Molecular, Cell & Systems Biology