Evidence map›Paper›PMID 25378658›Full record

ArticleJournal of lipid research2015

Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis.

Diana M Shih, Zeneng Wang, Richard Lee, Yonghong Meng, Nam Che, Sarada Charugundla, Hannah Qi, Judy Wu, Calvin Pan, J Mark Brown and 5 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of lipid research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
180citing papers in PubMed, 5 pooled it
11.0field-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

180 citing papers in PubMed, 5 syntheses or guidelines pooled it, 331 citations in OpenAlex.

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120 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

15 authors at 4 institutions in 1 country.

Diana M ShihDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Zeneng WangDepartment of Cellular and Molecular Medicine (NC10), Cleveland Clinic Lerner Research Institute, Cleveland, OH.
Richard LeeIsis Pharmaceuticals, Carlsbad, CA.
Yonghong MengDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Nam CheDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Sarada CharugundlaDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Hannah QiDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Judy WuDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Calvin PanDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
J Mark BrownDepartment of Cellular and Molecular Medicine (NC10), Cleveland Clinic Lerner Research Institute, Cleveland, OH.
Thomas VallimDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Brian J BennettDepartment of Genetics, University of North Carolina, Chapel Hill, NC.
Mark GrahamIsis Pharmaceuticals, Carlsbad, CA.
Stanley L HazenDepartment of Cellular and Molecular Medicine (NC10), Cleveland Clinic Lerner Research Institute, Cleveland, OH.
Aldons J LusisDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA Departments of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
University of California, Los Angeles · USCleveland Clinic Lerner College of Medicine · USIonis Pharmaceuticals (United States) · USUniversity of North Carolina at Chapel Hill · 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 REUE, KAREN · 1985 to 2019
$50.2M
Functional Cardio-MetabolomicsP20HL113452 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2012 to 2016
$4.8M
NHLBI NIH HHS HL113452NHLBI NIH HHS HL28481NHLBI NIH HHS HL30568NHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01 HL030568NHLBI NIH HHS P20 HL113452
6 · The paper itself

Abstract

We performed silencing and overexpression studies of flavin containing monooxygenase (FMO) 3 in hyperlipidemic mouse models to examine its effects on trimethylamine N-oxide (TMAO) levels and atherosclerosis. Knockdown of hepatic FMO3 in LDL receptor knockout mice using an antisense oligonucleotide resulted in decreased circulating TMAO levels and atherosclerosis. Surprisingly, we also observed significant decreases in hepatic lipids and in levels of plasma lipids, ketone bodies, glucose, and insulin. FMO3 overexpression in transgenic mice, on the other hand, increased hepatic and plasma lipids. Global gene expression analyses suggested that these effects of FMO3 on lipogenesis and gluconeogenesis may be mediated through the PPARα and Kruppel-like factor 15 pathways. In vivo and in vitro results were consistent with the concept that the effects were mediated directly by FMO3 rather than trimethylamine/TMAO; in particular, overexpression of FMO3 in the human hepatoma cell line, Hep3B, resulted in significantly increased glucose secretion and lipogenesis. Our results indicate a major role for FMO3 in modulating glucose and lipid homeostasis in vivo, and they suggest that pharmacologic inhibition of FMO3 to reduce TMAO levels would be confounded by metabolic interactions.

Indexed as

Lipid MetabolismAnimalsAtherosclerosisBile Acids and SaltsCell Line, TumorDiet, WesternDNA-Binding ProteinsFecesFemaleGene Expression Regulation, EnzymologicGene Knockdown TechniquesGene Knockout TechniquesGlucoseHomeostasisHumansInsulinBile Acids and Saltsdimethylaniline monooxygenase (N-oxide forming)DNA-Binding ProteinsGlucoseInsulinKlf15 protein, mouseKruppel-Like Transcription FactorsLipoproteinsMethylaminesOxygenasesPPAR alphaReceptors, LDLTranscription Factorstrimethylaminetrimethyloxaminetrimethylamine-N-oxide • peroxisome proliferator-activated receptor alpha • insulin

Identifiers

PMID25378658
PMCPMC4274068
OpenAlexW2163604084

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.