ArticleCell reports2017
The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue.
Erratum issued Registry-linked trialOpen access · goldAbstract read
In one paragraph
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04308473 (Analysis of MicroBial Metabolites After Eating Refined Food), which is not on this map. Cited by 164 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
164citing papers in PubMed, 1 pooled it
10.2field-weighted citation impact, top 1% of its field
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.
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.
Analysis of MicroBial Metabolites After Eating Refined Food
Who cites it
164 citing papers in PubMed, 1 synthesis or guideline pooled it, 284 citations in OpenAlex.
- The microbiome-derived metabolite trimethylamine N-oxide is associated with chronic kidney disease risk.Applied microbiology and biotechnology · 2025Pooled it
- Gut Microbiome and Metabolome Alterations in Overweight or Obese Adult Population after Weight-LossInternational journal of molecular sciences · 2024Trial
- Impact of Hypoxia-Hyperoxia Exposures on Cardiometabolic Risk Factors and TMAO Levels in Patients with Metabolic Syndrome.International journal of molecular sciences · 2023Trial
- Circulating Gut Microbiota Metabolite Trimethylamine N-Oxide (TMAO) and Changes in Bone Density in Response to Weight Loss Diets: The POUNDS Lost Trial.Diabetes care · 2019Trial
- Trial
- Trial
- Microbial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis Potential.Circulation research · 2018Trial
- Longevity-driven hepatic transcriptional programs mediate resilience to diet-induced liver injury in Ames dwarf mice.GeroScience · 2026Article
- Trimethylamine-N-oxide: the microbial cue in immune-mediated disorders.Trends in endocrinology and metabolism: TEM · 2026Review
- Targeting the human gut microbiome: a comparative review of probiotics, prebiotics, synbiotics, and postbiotics.Journal of advanced research · 2026Review
- Article
- Gut microbiota, brown adipose tissue whitening, and obesity: nutritional modulators and metabolic crosstalk.Nutrition & metabolism · 2026Review
- Metabotherapy for intestinal disease: using metabolites to prevent and treat disorders of the gut.Nature reviews. Gastroenterology & hepatology · 2026Review
- Dietary choline intake during pregnancy and birth weight in a Chinese population: a cross-sectional study.Nutrition journal · 2026Observational
- Blood Focused-Metabolomics and Transcriptomics Uncover Non-Linear Risk Association of Inadequate Dietary Choline Intake-Linked Metabolic Stress with MASLD Through Amino Acid Biomarkers,International journal of molecular sciences · 2026Article
- Review
- Single- and Multi-Trait GWASs Combined with Genetic Parameter Estimation Reveal Candidate Genes for Body Conformation Traits in Sika Deer (Animals : an open access journal from MDPI · 2026Article
- Dysregulation of the Gut-Adipose Tissue-Liver Axis: a Possible Mechanism Behind the Relationship Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes.Current diabetes reports · 2026Review
- Trimethylamine N-oxide is elevated in postmenopausal women relative to age-matched men and premenopausal women among individuals with obesity.Experimental physiology · 2026Article
- Time Exposure and Fat Mass Reduction Drive Trimethylamine N-Oxide Modulation During a Very-Low-Energy Ketogenic Therapy (VLEKT) in Women with Obesity.Metabolites · 2026Article
104 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
38 authors at 9 institutions in 3 countries.
Rebecca C SchugarDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA.
Diana M ShihDepartments of Medicine, Microbiology, and Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Manya WarrierDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA.
Robert N HelsleyDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA.
Amy BurrowsDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA.
Daniel FergusonDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA.
Amanda L BrownDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA.
Anthony D GromovskyDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA.
Markus HeineDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
Arunachal ChatterjeeDepartment of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA.
Lin LiDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA.
Xinmin S LiDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA.
Zeneng WangDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA.
Belinda WillardDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA.
YongHong MengDepartments of Medicine, Microbiology, and Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Hanjun KimDepartments of Medicine, Microbiology, and Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Nam CheDepartments of Medicine, Microbiology, and Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Calvin PanDepartments of Medicine, Microbiology, and Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Richard G LeeCardiovascular Group, Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA 92010, USA.
Rosanne M CrookeCardiovascular Group, Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA 92010, USA.
Mark J GrahamCardiovascular Group, Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA 92010, USA.
Richard E MortonDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Carl D LangefeldDepartment of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA.
Swapan K DasDepartment of Endocrinology and Metabolism, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA.
Lawrence L RudelDepartment of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA.
Nizar ZeinDepartment of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, USA.
Arthur J McCulloughDepartment of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, USA.
Srinivasan DasarathyDepartment of Pathobiology, Cleveland Clinic, Cleveland, OH 44195, USA.
W H Wilson TangDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Bernadette O ErokwuDepartments of Radiology, Biomedical Engineering, and Pediatrics, Case Western Reserve University, Cleveland, OH 44195, USA.
Chris A FlaskDepartments of Radiology, Biomedical Engineering, and Pediatrics, Case Western Reserve University, Cleveland, OH 44195, USA.
Markku LaaksoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
Mete CivelekDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22904, USA.
Sathyamangla V Naga PrasadDepartment of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA.
Joerg HeerenDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
Aldons J LusisDepartments of Medicine, Microbiology, and Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Stanley L HazenDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
J Mark BrownDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: brownm5@ccf.org.
Cleveland Clinic · USUniversity of California, Los Angeles · USIonis Pharmaceuticals (United States) · USWake Forest University · USCase Western Reserve University · USKuopio University Hospital · FIUniversität Hamburg · DEUniversity Medical Center Hamburg-Eppendorf · DEUniversity of Virginia · US
Funding
ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2MSystems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 1985 to 2019
$50.2MTISSUE CULTURE COREP01HL049373 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI RUDEL, LAWRENCE L · 1993 to 2012
$23.8MProject Two - Exercise Training Decreases Alcohol Drinking by an FGF21-Dependent MechanismP50AA024333 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI LAURA E. NAGY · 2016 to 2026
$19.6MThe Cleveland Digestive Diseases Research Core Center (DDRCC)P30DK097948 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI AMITABH CHAK · 2015 to 2026
$15.6MGut Flora Metabolism of Dietary Phosphatidylcholine and CVDR01HL103866 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L · 2010 to 2023
$10.8MDiet, Gut Microbiota, and Heart FailureR01HL126827 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2016 to 2019
$3.1MDietary Choline, Gut Microbiota, and Susceptibility for Chronic Kidney DiseaseR01DK106000 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2015 to 2018
$2.8MMapping Diabetes Susceptibility by Expression Traits in African AmericansR01DK090111 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI DAS, SWAPAN KUMAR · 2011 to 2015
$2.5MEnzymatic Control of Trimethylamineoxide (TMAO)Induced AtherosclerosisR01HL122283 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BROWN, JONATHAN MARK · 2014 to 2018
$2.0MMicrobial Trimethylamine Lyases and AtherosclerosisR01HL130819 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI WANG, ZENENG · 2016 to 2019
$1.7MSystems genetics analysis of cardiometabolic trait loci in humans R00HL121172 · NHLBI · UNIVERSITY OF VIRGINIA · PI CIVELEK, METE · 2016 to 2018
$741kNHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01 HL030568NHLBI NIH HHS P01 HL049373NHLBI NIH HHS R00 HL096166NHLBI NIH HHS R00 HL121172NHLBI NIH HHS R01 HL103866NHLBI NIH HHS R01 HL122283NHLBI NIH HHS R01 HL126827NHLBI NIH HHS R01 HL130819NIAAA NIH HHS P50 AA024333NIDDK NIH HHS P30 DK097948NIDDK NIH HHS R01 DK090111NIDDK NIH HHS R01 DK106000
Abstract
Emerging evidence suggests that microbes resident in the human intestine represent a key environmental factor contributing to obesity-associated disorders. Here, we demonstrate that the gut microbiota-initiated trimethylamine N-oxide (TMAO)-generating pathway is linked to obesity and energy metabolism. In multiple clinical cohorts, systemic levels of TMAO were observed to strongly associate with type 2 diabetes. In addition, circulating TMAO levels were associated with obesity traits in the different inbred strains represented in the Hybrid Mouse Diversity Panel. Further, antisense oligonucleotide-mediated knockdown or genetic deletion of the TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) conferred protection against obesity in mice. Complimentary mouse and human studies indicate a negative regulatory role for FMO3 in the beiging of white adipose tissue. Collectively, our studies reveal a link between the TMAO-producing enzyme FMO3 and obesity and the beiging of white adipose tissue.
Indexed as
Adipocytes, BeigeAnimalsDiabetes Mellitus, Type 2FemaleGene ExpressionHumansMaleMethylaminesMiceMice, Inbred C57BLMice, KnockoutObesityOxygenasesSubcutaneous Fatdimethylaniline monooxygenase (N-oxide forming)MethylaminesOxygenasestrimethyloxamineadiposediabetesflavin-containing monooxygenase 3FMO3microbiotanutritionobesity
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Registered trials
NCT04308473ClinicalTrials.gov
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.