Evidence map›Paper›PMID 23312283›Full record

ArticleCell metabolism2013

Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation.

Brian J Bennett, Thomas Q de Aguiar Vallim, Zeneng Wang, Diana M Shih, Yonghong Meng, Jill Gregory, Hooman Allayee, Richard Lee, Mark Graham, Rosanne Crooke and 3 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Cell metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04510324 (Plant-Based Meat vs Animal "Red" Meat), which is not on this map. Cited by 594 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
594citing papers in PubMed, 8 pooled it
26.6field-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.

NCT04510324 nacompletednot on this mapstarted 2020, after this paper: background citation

Plant-Based Meat vs Animal "Red" Meat: a Randomized Cross-over Trial

TypeinterventionalSponsorMcGill University Health Centre/Research Institute of the McGill University Health CentreRan2020 to 2023Enrolled41ConditionsInflammatory ResponseArmsRed meat patties group, Plant-based patties group
3 · Its place in the literature

Who cites it

594 citing papers in PubMed, 8 syntheses or guidelines pooled it, 1,042 citations in OpenAlex.

  1. Effects of Weight Loss Interventions on Gut Microbiota-Derived Metabolites Linked to Cardiometabolic Health: A Systematic Review and Meta-Analysis.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Trial
  10. Trial
  11. Plasma Trimethylamine-Journal of the American Heart Association · 2023
    Trial
  12. Trial
  13. Gut microbes · 2026
    Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article

534 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 1 country.

Brian J BennettDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. brian_bennett@med.unc.edu
Thomas Q de Aguiar Vallim
Zeneng Wang
Diana M Shih
Yonghong Meng
Jill Gregory
Hooman Allayee
Richard Lee
Mark Graham
Rosanne Crooke
Peter A Edwards
Stanley L Hazen
Aldons J Lusis
University of California, Los Angeles · USCleveland Clinic · USIonis Pharmaceuticals (United States) · USUniversity of Southern California · US

Funding

ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2M
Systems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 1985 to 2019
$50.2M
Gut Flora Metabolism of Dietary Phosphatidylcholine and CVDR01HL103866 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L · 2010 to 2023
$10.8M
Functional Cardio-MetabolomicsP20HL113452 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2012 to 2016
$4.8M
Dissection of HDL function using mouse modelsR01HL094322 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2009 to 2013
$1.9M
Molecular Medicine Training ProgramT32GM088088 · NIGMS · CLEVELAND CLINIC LERNER COM-CWRU · PI SMITH, JONATHAN D · 2011 to 2020
$1.7M
High-Resolution Systems Genetic Studies of Atherosclerotic Lesion CompositionR00HL102223 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BENNETT, BRIAN JOSEPH · 2012 to 2014
$714k
High-Resolution Systems Genetic Studies of Atherosclerotic Lesion CompositionK99HL102223 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BENNETT, BRIAN JOSEPH · 2011 to 2011
$108k
Howard Hughes Medical InstituteNHLBI NIH HHS HL103866NHLBI NIH HHS HL113452NHLBI NIH HHS HL28481NHLBI NIH HHS HL30568NHLBI NIH HHS HL94322NHLBI NIH HHS K99 HL102223NHLBI NIH HHS K99/R00 HL102223NHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01 HL030568NHLBI NIH HHS P20 HL113452NHLBI NIH HHS R00 HL102223NHLBI NIH HHS R01 HL094322NHLBI NIH HHS R01 HL103866NIGMS NIH HHS T32 GM088088NIGMS NIH HHS T32GM088088
6 · The paper itself

Abstract

Circulating trimethylamine-N-oxide (TMAO) levels are strongly associated with atherosclerosis. We now examine genetic, dietary, and hormonal factors regulating TMAO levels. We demonstrate that two flavin mono-oxygenase family members, FMO1 and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to TMAO. Further, we show that FMO3 exhibits 10-fold higher specific activity than FMO1. FMO3 overexpression in mice significantly increases plasma TMAO levels while silencing FMO3 decreases TMAO levels. In both humans and mice, hepatic FMO3 expression is reduced in males compared to females. In mice, this reduction in FMO3 expression is due primarily to downregulation by androgens. FMO3 expression is induced by dietary bile acids by a mechanism that involves the farnesoid X receptor (FXR), a bile acid-activated nuclear receptor. Analysis of natural genetic variation among inbred strains of mice indicates that FMO3 and TMAO are significantly correlated, and TMAO levels explain 11% of the variation in atherosclerosis.

Indexed as

DietAndrogensAnimalsAtherosclerosisBase SequenceBile Acids and SaltsCholineDown-RegulationFemaleGene SilencingHEK293 CellsHumansMaleMethylaminesMiceMice, KnockoutAndrogensBile Acids and SaltsCholinedimethylaniline monooxygenase (N-oxide forming)MethylaminesOxygenasesReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and Nucleartrimethylaminetrimethyloxamine

Identifiers

PMID23312283
PMCPMC3771112
OpenAlexW2046971089

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.