Evidence map›Paper›PMID 30992568›Full record

ArticleNature chemical biology2019

Chemogenetics defines receptor-mediated functions of short chain free fatty acids.

Daniele Bolognini, Natasja Barki, Adrian J Butcher, Brian D Hudson, Eugenia Sergeev, Colin Molloy, Daryl Hodge, Sophie J Bradley, Christian Le Gouill, Michel Bouvier and 2 more

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 71 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Daniele BologniniCentre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.ORCID 0000-0003-0813-0865
Natasja BarkiCentre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Adrian J ButcherUK Dementia Research Institute at the University of Cambridge, Cambridge, UK.
Brian D HudsonCentre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.ORCID 0000-0001-7059-0091
Eugenia SergeevCentre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Colin MolloyCentre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Daryl HodgeCentre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Sophie J BradleyCentre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Christian Le GouillDepartment of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer, Université de Montreal, Montreal, Quebec, Canada.
Michel BouvierDepartment of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer, Université de Montreal, Montreal, Quebec, Canada.ORCID 0000-0003-1128-0100
Andrew B TobinCentre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. Andrew.Tobin@glasgow.ac.uk.ORCID 0000-0002-1807-3123
Graeme MilliganCentre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. Graeme.Milligan@glasgow.ac.uk.ORCID 0000-0002-6946-3519
University of Glasgow · GBInstitute for Research in Immunology and Cancer · CAUniversity of Cambridge · GB

Funding

Medical Research Council MR/P019366/1
6 · The paper itself

Abstract

Differentiating actions of short chain fatty acids (SCFAs) at free fatty acid receptor 2 (FFA2) from other free fatty acid-responsive receptors and from non-receptor-mediated effects has been challenging. Using a novel chemogenetic and knock-in strategy, whereby an engineered variant of FFA2 (FFA2-DREADD) that is unresponsive to natural SCFAs but is instead activated by sorbic acid replaced the wild-type receptor, we determined that activation of FFA2 in differentiated adipocytes and colonic crypt enteroendocrine cells of mouse accounts fully for SCFA-regulated lipolysis and release of the incretin glucagon-like peptide-1 (GLP-1), respectively. In vivo studies confirmed the specific role of FFA2 in GLP-1 release and also demonstrated a direct role for FFA2 in accelerating gut transit. Thereby, we establish the general principle that such a chemogenetic knock-in strategy can successfully define novel G-protein-coupled receptor (GPCR) biology and provide both target validation and establish therapeutic potential of a 'hard to target' GPCR.

Indexed as

AnimalsFatty Acids, VolatileHumansMiceReceptors, Cell SurfaceReceptors, G-Protein-CoupledFatty Acids, VolatileFFAR2 protein, humanFfar2 protein, mouseReceptors, Cell SurfaceReceptors, G-Protein-Coupled

Identifiers

PMID30992568
OpenAlexW2937428609

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.