Evidence map›Paper›PMID 33507883›Full record

ArticleThe Journal of clinical investigation2021

An abundant biliary metabolite derived from dietary omega-3 polyunsaturated fatty acids regulates triglycerides.

Trisha J Grevengoed, Samuel Aj Trammell, Jens S Svenningsen, Mikhail V Makarov, Thomas Svava Nielsen, Jens Christian Brings Jacobsen, Jonas T Treebak, Philip C Calder, Marie E Migaud, Benjamin F Cravatt and 1 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.5field-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

17 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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  7. Disorders of fatty acid homeostasis.Journal of inherited metabolic disease · 2025
    Review
  8. Article
  9. Article
  10. Omega-3 (Nutrients · 2024
    Review
  11. Review
  12. Fish oil supplementation modifies the genetic potential for blood lipids.medRxiv : the preprint server for health sciences · 2023
    Article
  13. Review
  14. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 3 countries.

Trisha J GrevengoedNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Samuel Aj TrammellNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jens S SvenningsenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Mikhail V MakarovMitchell Cancer Institute, Department of Pharmacology, University of South Alabama, Mobile, Alabama, USA.
Thomas Svava NielsenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jens Christian Brings JacobsenDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jonas T TreebakNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Philip C CalderFaculty of Medicine, University of Southampton, Southampton, United Kingdom.
Marie E MigaudMitchell Cancer Institute, Department of Pharmacology, University of South Alabama, Mobile, Alabama, USA.
Benjamin F CravattDepartments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, California, USA.
Matthew P GillumNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
University of Copenhagen · DKUSA Mitchell Cancer Institute · USScripps Research Institute · USUniversity Hospital Southampton NHS Foundation Trust · GB

Funding

CHEMOPROTEOMIC METHODS FOR SERINE HYDROLASE INHIBITOR DEVELOPMENTR01DA033760 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI CRAVATT, BENJAMIN F, SCAMPAVIA, LOUIS DANIEL · 2012 to 2021
$5.1M
NIDA NIH HHS R01 DA033760
6 · The paper itself

Abstract

Omega-3 fatty acids from fish oil reduce triglyceride levels in mammals, yet the mechanisms underlying this effect have not been fully clarified, despite the clinical use of omega-3 ethyl esters to treat severe hypertriglyceridemia and reduce cardiovascular disease risk in humans. Here, we identified in bile a class of hypotriglyceridemic omega-3 fatty acid-derived N-acyl taurines (NATs) that, after dietary omega-3 fatty acid supplementation, increased to concentrations similar to those of steroidal bile acids. The biliary docosahexaenoic acid-containing (DHA-containing) NAT C22:6 NAT was increased in human and mouse plasma after dietary omega-3 fatty acid supplementation and potently inhibited intestinal triacylglycerol hydrolysis and lipid absorption. Supporting this observation, genetic elevation of endogenous NAT levels in mice impaired lipid absorption, whereas selective augmentation of C22:6 NAT levels protected against hypertriglyceridemia and fatty liver. When administered pharmacologically, C22:6 NAT accumulated in bile and reduced high-fat diet-induced, but not sucrose-induced, hepatic lipid accumulation in mice, suggesting that C22:6 NAT is a negative feedback mediator that limits excess intestinal lipid absorption. Thus, biliary omega-3 NATs may contribute to the hypotriglyceridemic mechanism of action of fish oil and could influence the design of more potent omega-3 fatty acid-based therapeutics.

Indexed as

AmidohydrolasesAnimalsBileDisease Models, AnimalDocosahexaenoic AcidsFatty Acid Amide HydrolasesFatty Acids, Omega-3Fatty LiverHumansHypertriglyceridemiaHypolipidemic AgentsIntestinal AbsorptionLipid MetabolismLiverMaleMiceAmidohydrolasesDocosahexaenoic AcidsFatty Acid Amide HydrolasesFatty Acids, Omega-3Hypolipidemic AgentsMutant ProteinsTaurineTriglyceridesEndocrinologyFatty acid oxidationGastroenterologyLipoproteins

Identifiers

PMID33507883
PMCPMC7954602
OpenAlexW3125136009

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.