Evidence map›Paper›PMID 38265935›Full record

ArticleCell reports2024

Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting.

Milton Pereira, Jonathan Liang, Joy Edwards-Hicks, Allison M Meadows, Christine Hinz, Sonia Liggi, Matthias Hepprich, Jonathan M Mudry, Kim Han, Julian L Griffin and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
15.0field-weighted citation impact, top 1% 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

42 citing papers in PubMed, 64 citations in OpenAlex.

  1. Arachidonic Acid Structure and Synthesis.Reviews of physiology, biochemistry and pharmacology · 2027
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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

14 authors at 5 institutions in 3 countries.

Milton PereiraDepartment of Veterinary Medicine, University of Cambridge, Cambridge, UK.
Jonathan LiangDepartment of Veterinary Medicine, University of Cambridge, Cambridge, UK; Signaling Systems Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Joy Edwards-HicksThe Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge, Cambridge, UK.
Allison M MeadowsLaboratory of Mitochondrial Biology and Metabolism, National Heart, Lung and Blood Institute (NHLBI), NIH, Bethesda, MD, USA; Department of Biochemistry, University of Cambridge, Cambridge, UK.
Christine HinzDepartment of Biochemistry, University of Cambridge, Cambridge, UK.
Sonia LiggiDepartment of Biochemistry, University of Cambridge, Cambridge, UK.
Matthias HepprichUniversity Hospital Basel, Basel, Switzerland.
Jonathan M MudryCantonal Hospital of Freiburg, Freiburg, Switzerland.
Kim HanLaboratory of Mitochondrial Biology and Metabolism, National Heart, Lung and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
Julian L GriffinDepartment of Biochemistry, University of Cambridge, Cambridge, UK.
Iain FraserSignaling Systems Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Michael N SackLaboratory of Mitochondrial Biology and Metabolism, National Heart, Lung and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
Christoph HessThe Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge, Cambridge, UK.
Clare E BryantDepartment of Veterinary Medicine, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK. Electronic address: ceb27@cam.ac.uk.
University of Cambridge · GBNational Heart Lung and Blood Institute · USNational Institutes of Health · USHFR Freiburg Kantonsspital · CHUniversity Hospital of Basel · CH

Funding

Mitochondrial Biology in DiseaseZIAHL005102 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI SACK, MICHAEL · 2009 to 2025
$22.7M
Mitochondrial biology in diabetesZIAHL005199 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI SACK, MICHAEL · 2009 to 2025
$17.2M
RNAi Screening in Hematopoietic CellsZIAAI001106 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FRASER, IAIN · 2009 to 2025
$12.4M
Analysis of Innate Immune Signaling NetworksZIAAI001107 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FRASER, IAIN · 2009 to 2025
$11.9M
Mitochondrial biology in diabetesZ01HL005199 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI SACK, MICHAEL · 2007 to 2008
$3.5M
Intramural NIH HHS Z01 HL005199Intramural NIH HHS ZIA HL005199Wellcome Trust
6 · The paper itself

Abstract

Elevated interleukin (IL)-1β levels, NLRP3 inflammasome activity, and systemic inflammation are hallmarks of chronic metabolic inflammatory syndromes, but the mechanistic basis for this is unclear. Here, we show that levels of plasma IL-1β are lower in fasting compared to fed subjects, while the lipid arachidonic acid (AA) is elevated. Lipid profiling of NLRP3-stimulated mouse macrophages shows enhanced AA production and an NLRP3-dependent eicosanoid signature. Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs decreases eicosanoid, but not AA, production. It also reduces both IL-1β and IL-18 production in response to NLRP3 activation. AA inhibits NLRP3 inflammasome activity in human and mouse macrophages. Mechanistically, AA inhibits phospholipase C activity to reduce JNK1 stimulation and hence NLRP3 activity. These data show that AA is an important physiological regulator of the NLRP3 inflammasome and explains why fasting reduces systemic inflammation and also suggests a mechanism to explain how nonsteroidal anti-inflammatory drugs work.

Indexed as

InflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinAnimalsAnti-Inflammatory Agents, Non-SteroidalArachidonic AcidEicosanoidsFastingHumansInflammationInterleukin-1betaMiceAnti-Inflammatory Agents, Non-SteroidalArachidonic AcidEicosanoidsInflammasomesInterleukin-1betaNLR Family, Pyrin Domain-Containing 3 ProteinCP: ImmunologyCP: MetabolismeicosanoidsinflammasomeinflammationlipidomicsmetaflammationNLRP3prostaglandins

Identifiers

PMID38265935
PMCPMC10940735
OpenAlexW4391154523

What OpenQuestion holds

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Registered trials

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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.