Evidence map›Paper›PMID 25600868›Full record

ArticleCell reports2015

The TMAO-Generating Enzyme Flavin Monooxygenase 3 Is a Central Regulator of Cholesterol Balance.

Manya Warrier, Diana M Shih, Amy C Burrows, Daniel Ferguson, Anthony D Gromovsky, Amanda L Brown, Stephanie Marshall, Allison McDaniel, Rebecca C Schugar, Zeneng Wang and 17 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2015. 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 227 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
227citing papers in PubMed, 4 pooled it
37.8field-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

227 citing papers in PubMed, 4 syntheses or guidelines pooled it, 411 citations in OpenAlex.

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  11. Trimethylamine-N-oxide: the microbial cue in immune-mediated disorders.Trends in endocrinology and metabolism: TEM · 2026
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167 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

27 authors at 9 institutions in 2 countries.

Manya WarrierDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
Diana M ShihDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Amy C BurrowsDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
Daniel FergusonDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
Anthony D GromovskyDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
Amanda L BrownDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
Stephanie MarshallDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
Allison McDanielDepartments of Pathology and Biostatistics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Rebecca C SchugarDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
Zeneng WangDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
Jessica SacksDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
Xin RongDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Thomas de Aguiar VallimDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jeff ChouDepartments of Pathology and Biostatistics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Pavlina T IvanovaDepartments of Pharmacology and Biochemistry, The Vanderbilt Institute of Chemical Biology, Nashville, TN 37232, USA.
David S MyersDepartments of Pharmacology and Biochemistry, The Vanderbilt Institute of Chemical Biology, Nashville, TN 37232, USA.
H Alex BrownDepartments of Pharmacology and Biochemistry, The Vanderbilt Institute of Chemical Biology, Nashville, TN 37232, USA.
Richard G LeeCardiovascular Group, Antisense Drug Discovery, Isis Pharmaceuticals, Inc., Carlsbad, CA 92010, USA.
Rosanne M CrookeCardiovascular Group, Antisense Drug Discovery, Isis Pharmaceuticals, Inc., Carlsbad, CA 92010, USA.
Mark J GrahamCardiovascular Group, Antisense Drug Discovery, Isis Pharmaceuticals, Inc., Carlsbad, CA 92010, USA.
Xiuli LiuDepartment of Anatomical Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Paolo PariniClinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, 141 86 Stockholm, Sweden.
Peter TontonozHoward Hughes Medical Institute; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Aldon J LusisDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Stanley L HazenDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
Ryan E TemelSaha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536-0509, USA.
J Mark BrownDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA. Electronic address: brownm5@ccf.org.
Cleveland Clinic Lerner College of Medicine · USUniversity of California, Los Angeles · USIonis Pharmaceuticals (United States) · USVanderbilt University · USWake Forest University · USCleveland Clinic · USHoward Hughes Medical Institute · USKarolinska University Hospital · SEUniversity of Kentucky · US

Funding

STEROL LIPIDSU54GM069338 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DENNIS, EDWARD A · 2003 to 2013
$72.2M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024989 · NCRR · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B · 2007 to 2011
$53.7M
Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
Gut Flora Metabolism of Dietary Phosphatidylcholine and CVDR01HL103866 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L · 2010 to 2023
$10.8M
NUCLEAR RECEPTOR SIGNALING PATHWAYS IN ATHEROGENESISR01HL066088 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TONTONOZ, PETER J · 2001 to 2018
$5.4M
Functional Cardio-MetabolomicsP20HL113452 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2012 to 2016
$4.8M
Enzymatic Control of Trimethylamineoxide (TMAO)Induced AtherosclerosisR01HL122283 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BROWN, JONATHAN MARK · 2014 to 2018
$2.0M
Integrative Lipid Metabolism, Inflammation, and Chronic DiseasesT32HL091797 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI PARKS, JOHN S · 2008 to 2017
$1.8M
Mechanisms Regulating Non-biliary Fecal Sterol LossR00HL096166 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI BROWN, JONATHAN MARK · 2011 to 2013
$733k
NCATS NIH HHS UL1 TR000439NCRR NIH HHS UL1 RR024989NHLBI NIH HHS P20 HL113452NHLBI NIH HHS R00 HL096166NHLBI NIH HHS R01 HL066088NHLBI NIH HHS R01 HL103866NHLBI NIH HHS R01 HL122283NHLBI NIH HHS T32 HL091797NIDDK NIH HHS P30 DK063491NIGMS NIH HHS U54 GM069338
6 · The paper itself

Abstract

Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide (TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here, we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT) and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic endoplasmic reticulum (ER) stress and inflammation in part by decreasing hepatic oxysterol levels and subsequent LXR activation. FMO3 is thus identified as a central integrator of hepatic cholesterol and triacylglycerol metabolism, inflammation, and ER stress. These studies suggest that the gut microbiota-driven TMA/FMO3/TMAO pathway is a key regulator of lipid metabolism and inflammation.

Identifiers

PMID25600868
PMCPMC4501903
OpenAlexW2046316092

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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.