Evidence map›Paper›PMID 34083384›Full record

Trial reportGut2022

Decoy bypass for appetite suppression in obese adults: role of synergistic nutrient sensing receptors GPR84 and FFAR4 on colonic endocrine cells.

Madusha Peiris, Rubina Aktar, David Reed, Vincent Cibert-Goton, Ausra Zdanaviciene, Writaja Halder, Adam Robinow, Simon Corke, Harween Dogra, Charles H Knowles and 1 more

2 registry-linked trialsOpen access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Gut, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.3field-weighted citation impact, top 12% 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.

NCT07491835 nacompletedstarted 2023, after this paper: background citation

The Effect of Nutrients on Regulating Appetite - a Dosing Study

Ran2023Enrolled16Registered outcomes3Posted comparisons0ConditionsAppetite Regulation, Obesity & OverweightArmsArm 1 (Medium Dose): 250mg DIM and 1050mg Perilla oil in GuardCap™ colon-targeted capsules, activating GPR84 and FFA4 to stimulate PYY and GLP-1 release., Arm 2 (Low Dose): 125mg DIM and 525mg Perilla oil in GuardCap™ colon-targeted capsules, activating GPR84 and FFA4 to stimulate PYY and GLP-1 release.
Open the trial in the graph
NCT04292236 nacompletednot on this map

The Effect of Food Supplements on Food Intake and Gut Hormone Levels

TypeinterventionalSponsorQueen Mary University of LondonRan2019 to 2019Enrolled20ConditionsObesity, Endocrine, Obesity, AppetiteArmsLauric Acid, Perilla Oil and Diindolylmethane
3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Advances in colon-targeted drug technologies.Current opinion in gastroenterology · 2025
    Review
  9. Review
  10. Sensing of luminal contents and downstream modulation of GI function.JGH open : an open access journal of gastroenterology and hepatology · 2024
    Review
  11. Article
  12. Article
  13. Intestinal Enteroendocrine Cells: Present and Future Druggable Targets.International journal of molecular sciences · 2023
    Review
  14. Article
  15. Article
  16. Review
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

11 authors at 2 institutions in 2 countries.

Madusha PeirisCentre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK m.peiris@qmul.ac.uk.ORCID 0000-0003-4429-5931
Rubina AktarCentre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
David ReedGastrointestinal Diseases Research, Queen's University, Kingston, Queensland, Canada.
Vincent Cibert-GotonCentre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Ausra ZdanavicieneCentre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Writaja HalderCentre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Adam RobinowCentre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Simon CorkeCentre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Harween DograCentre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Charles H KnowlesCentre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Ashley BlackshawCentre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Queen Mary University of London · GBQueen's University · CA

Funding

Biotechnology and Biological Sciences Research Council BBS/E/F/000PR10355Wellcome Trust
6 · The paper itself

Abstract

objectiveColonic enteroendocrine cells (EECs) store and release potent anorectic hormones that are key regulators of satiety. EECs express multiple nutrient sensing receptors, particularly for medium-chain fatty acids (MCFAs): GPR84 and FFAR4. Here we show a non-surgical approach with targeted colonic delivery of MCFA, which induces EEC and neuronal activation leading to anorectic effects.

designA randomised, double-blind, placebo-controlled, cross-over study was performed in obese adults given combined GPR84 and FFAR4 agonists in colonic release capsules before meals. We measured serum hormones, energy intake and appetite perception. Cell type, activation by agonists and hormone/serotonin release were determined in human colonic explants. Mouse colonic afferent nerve responses to nutrients/mediators were recorded electrophysiologically.

resultsSubjects receiving GPR84 and FFAR4 agonists had reduced overall calorific intake and increased postprandial levels of PYY versus placebo. Receptors including GPR84 and FFAR4 were coexpressed on human colonic EEC. Activation of GPR84 exclusively induced intracellular pERK, whereas FFAR4 selectively activated pCaMKII. Coactivation of GPR84 and FFAR4 induced both phosphoproteins, and superadditive release of GLP-1 and PYY. Nutrients and hormones convergently activated murine colonic afterent nerves via GLP-1, Y2 and 5-HT3 receptors.

conclusionsColonic GPR84 and FFAR4 agonists reduce energy intake and increase postprandial PYY in obese adults. Human colonic EECs coexpress these receptors, which activate cells via parallel intracellular pathways and synergistically evoke hormone release. Further synergism occurs in sensory nerve responses to MCFA and EEC mediators. Thus, synergistic activation of colonic endocrine cells via nutrient receptors is an important target for metabolic regulation. TRAIL REGISTRATION NUMBER: NCT04292236.

Indexed as

Appetite DepressantsAnimalsAppetiteCross-Over StudiesEnteroendocrine CellsGlucagon-Like Peptide 1HumansMiceNutrientsObesityReceptors, G-Protein-CoupledAppetite DepressantsGlucagon-Like Peptide 1GPR84 protein, humanGpr84 protein, mouseNutrientsReceptors, G-Protein-Coupledappetitegut hormonesneuroendocrine cellsobesity

Identifiers

PMID34083384
PMCPMC8995825
OpenAlexW3165619198

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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 Socratic graph.