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, Peter A Edwards, Stanley L Hazen, Aldons J Lusis, 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, Peter A Edwards, Stanley L Hazen, Aldons J Lusis
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.
Copyright © 2013 Elsevier Inc. All rights reserved.
Figures
![Figure 1. FMO3 is the Major FMO…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3771112/bin/nihms431767f1.jpg)
Figure 2. Modulation of Hepatic FMO3 levels…
Figure 2. Modulation of Hepatic FMO3 levels in Mice Regulates Plasma TMAO Levels
(A–C) FMO3…
Figure 3. Sex and Dietary Choline Regulate…
Figure 3. Sex and Dietary Choline Regulate Hepatic FMO3 Expression and Plasma TMAO Levels in…
Figure 4. Gonadal Hormones Regulate Hepatic FMO3…
Figure 4. Gonadal Hormones Regulate Hepatic FMO3 Expression and Plasma TMAO Levels
(A–C) Male and…
Figure 5. Dietary Cholic Acid Induces Fmo3…
Figure 5. Dietary Cholic Acid Induces Fmo3 Expression and TMAO Levels in Common Inbred Mouse…
Figure 6. FMO3 is an FXR Target…
Figure 6. FMO3 is an FXR Target Gene and FXR Activation Induces FMO3 and Increases…
Figure 7. Natural Genetic Variation of Hepatic…
Figure 7. Natural Genetic Variation of Hepatic FMO3, Plasma TMAO Levels and Atherosclerosis among Common…
- Dioxin-like pollutants increase hepatic flavin containing monooxygenase (FMO3) expression to promote synthesis of the pro-atherogenic nutrient biomarker trimethylamine N-oxide from dietary precursors.Petriello MC, Hoffman JB, Sunkara M, Wahlang B, Perkins JT, Morris AJ, Hennig B. Petriello MC, et al. J Nutr Biochem. 2016 Jul;33:145-53. doi: 10.1016/j.jnutbio.2016.03.016. Epub 2016 Apr 1. J Nutr Biochem. 2016. PMID: 27155921 Free PMC article.
- Genetic Deficiency of Flavin-Containing Monooxygenase 3 ( Fmo3) Protects Against Thrombosis but Has Only a Minor Effect on Plasma Lipid Levels-Brief Report.Shih DM, Zhu W, Schugar RC, Meng Y, Jia X, Miikeda A, Wang Z, Zieger M, Lee R, Graham M, Allayee H, Cantor RM, Mueller C, Brown JM, Hazen SL, Lusis AJ. Shih DM, et al. Arterioscler Thromb Vasc Biol. 2019 Jun;39(6):1045-1054. doi: 10.1161/ATVBAHA.119.312592. Arterioscler Thromb Vasc Biol. 2019. PMID: 31070450 Free PMC article.
- FMO3 and its metabolite TMAO contribute to the formation of gallstones.Chen Y, Weng Z, Liu Q, Shao W, Guo W, Chen C, Jiao L, Wang Q, Lu Q, Sun H, Gu A, Hu H, Jiang Z. Chen Y, et al. Biochim Biophys Acta Mol Basis Dis. 2019 Oct 1;1865(10):2576-2585. doi: 10.1016/j.bbadis.2019.06.016. Epub 2019 Jun 26. Biochim Biophys Acta Mol Basis Dis. 2019. PMID: 31251986
- Trimethylamine N-Oxide: A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function.Canyelles M, Tondo M, Cedó L, Farràs M, Escolà-Gil JC, Blanco-Vaca F. Canyelles M, et al. Int J Mol Sci. 2018 Oct 19;19(10):3228. doi: 10.3390/ijms19103228. Int J Mol Sci. 2018. PMID: 30347638 Free PMC article. Review.
- Trimethylamine-N-oxide: a link between the gut microbiome, bile acid metabolism, and atherosclerosis.Wilson A, McLean C, Kim RB. Wilson A, et al. Curr Opin Lipidol. 2016 Apr;27(2):148-54. doi: 10.1097/MOL.0000000000000274. Curr Opin Lipidol. 2016. PMID: 26959704 Review.
- Trimethylamine N-Oxide Concentration and Blood Pressure in Young Healthy Men and Women: A Replicated Crossover Study.Rowland SN, Heaney LM, Da Boit M, Bailey SJ. Rowland SN, et al. Metabolites. 2023 Jul 24;13(7):876. doi: 10.3390/metabo13070876. Metabolites. 2023. PMID: 37512583 Free PMC article.
- Upregulation of Taurine Biosynthesis and Bile Acid Conjugation with Taurine through FXR in a Mouse Model with Human-like Bile Acid Composition.Miyazaki T, Ueda H, Ikegami T, Honda A. Miyazaki T, et al. Metabolites. 2023 Jul 5;13(7):824. doi: 10.3390/metabo13070824. Metabolites. 2023. PMID: 37512531 Free PMC article.
- Interaction between gut microbiota metabolites and dietary components in lipid metabolism and metabolic diseases.Basnet TB, Gc S, Basnet R, Fatima S, Safdar M, Sehar B, Alsubaie ASR, Zeb F. Basnet TB, et al. Access Microbiol. 2023 Jun 23;5(6):acmi000403. doi: 10.1099/acmi.0.000403. eCollection 2023. Access Microbiol. 2023. PMID: 37424550 Free PMC article. Review.
- Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease.Gabriel CL, Ferguson JF. Gabriel CL, et al. Circ Res. 2023 Jun 9;132(12):1674-1691. doi: 10.1161/CIRCRESAHA.123.322055. Epub 2023 Jun 8. Circ Res. 2023. PMID: 37289901 Review.
- Gut microbiota-derived trimethylamine N-oxide is associated with the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease: a systematic review and dose-response meta-analysis.Li Y, Lu H, Guo J, Zhang M, Zheng H, Liu Y, Liu W. Li Y, et al. Ann Med. 2023 Dec;55(1):2215542. doi: 10.1080/07853890.2023.2215542. Ann Med. 2023. PMID: 37246850 Free PMC article.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Androgens / pharmacology
- Animals
- Atherosclerosis / genetics
- Atherosclerosis / metabolism*
- Atherosclerosis / pathology
- Base Sequence
- Bile Acids and Salts
- Choline / metabolism
- Diet*
- Down-Regulation / drug effects
- Female
- Gene Silencing
- HEK293 Cells
- Humans
- Male
- Methylamines / blood*
- Methylamines / metabolism
- Mice
- Mice, Knockout
- Oxygenases / genetics
- Oxygenases / metabolism
- Polymorphism, Single Nucleotide
- Receptors, Cytoplasmic and Nuclear / genetics
- Receptors, Cytoplasmic and Nuclear / metabolism
- Sex Factors
- Androgens
- Bile Acids and Salts
- Methylamines
- Receptors, Cytoplasmic and Nuclear
- farnesoid X-activated receptor
- Oxygenases
- dimethylaniline monooxygenase (N-oxide forming)
- trimethyloxamine
- trimethylamine
- Choline
- R01 HL094322/HL/NHLBI NIH HHS/United States
- R01 HL103866/HL/NHLBI NIH HHS/United States
- P01 HL028481/HL/NHLBI NIH HHS/United States
- P20 HL113452/HL/NHLBI NIH HHS/United States
- T32GM088088/GM/NIGMS NIH HHS/United States
- HL94322/HL/NHLBI NIH HHS/United States
- HL30568/HL/NHLBI NIH HHS/United States
- R00 HL102223/HL/NHLBI NIH HHS/United States
- P01 HL030568/HL/NHLBI NIH HHS/United States
- K99 HL102223/HL/NHLBI NIH HHS/United States
- K99/R00 HL102223/HL/NHLBI NIH HHS/United States
- HL28481/HL/NHLBI NIH HHS/United States
- HHMI/Howard Hughes Medical Institute/United States
- HL103866/HL/NHLBI NIH HHS/United States
- T32 GM088088/GM/NIGMS NIH HHS/United States
- HL113452/HL/NHLBI NIH HHS/United States
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Research Materials
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 2. Modulation of Hepatic FMO3 levels…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3771112/bin/nihms431767f2.jpg)
Figure 3. Sex and Dietary Choline Regulate…
Figure 3. Sex and Dietary Choline Regulate Hepatic FMO3 Expression and Plasma TMAO Levels in…
Figure 4. Gonadal Hormones Regulate Hepatic FMO3…
Figure 4. Gonadal Hormones Regulate Hepatic FMO3 Expression and Plasma TMAO Levels
(A–C) Male and…
Figure 5. Dietary Cholic Acid Induces Fmo3…
Figure 5. Dietary Cholic Acid Induces Fmo3 Expression and TMAO Levels in Common Inbred Mouse…
Figure 6. FMO3 is an FXR Target…
Figure 6. FMO3 is an FXR Target Gene and FXR Activation Induces FMO3 and Increases…
Figure 7. Natural Genetic Variation of Hepatic…
Figure 7. Natural Genetic Variation of Hepatic FMO3, Plasma TMAO Levels and Atherosclerosis among Common…
- Dioxin-like pollutants increase hepatic flavin containing monooxygenase (FMO3) expression to promote synthesis of the pro-atherogenic nutrient biomarker trimethylamine N-oxide from dietary precursors.Petriello MC, Hoffman JB, Sunkara M, Wahlang B, Perkins JT, Morris AJ, Hennig B. Petriello MC, et al. J Nutr Biochem. 2016 Jul;33:145-53. doi: 10.1016/j.jnutbio.2016.03.016. Epub 2016 Apr 1. J Nutr Biochem. 2016. PMID: 27155921 Free PMC article.
- Genetic Deficiency of Flavin-Containing Monooxygenase 3 ( Fmo3) Protects Against Thrombosis but Has Only a Minor Effect on Plasma Lipid Levels-Brief Report.Shih DM, Zhu W, Schugar RC, Meng Y, Jia X, Miikeda A, Wang Z, Zieger M, Lee R, Graham M, Allayee H, Cantor RM, Mueller C, Brown JM, Hazen SL, Lusis AJ. Shih DM, et al. Arterioscler Thromb Vasc Biol. 2019 Jun;39(6):1045-1054. doi: 10.1161/ATVBAHA.119.312592. Arterioscler Thromb Vasc Biol. 2019. PMID: 31070450 Free PMC article.
- FMO3 and its metabolite TMAO contribute to the formation of gallstones.Chen Y, Weng Z, Liu Q, Shao W, Guo W, Chen C, Jiao L, Wang Q, Lu Q, Sun H, Gu A, Hu H, Jiang Z. Chen Y, et al. Biochim Biophys Acta Mol Basis Dis. 2019 Oct 1;1865(10):2576-2585. doi: 10.1016/j.bbadis.2019.06.016. Epub 2019 Jun 26. Biochim Biophys Acta Mol Basis Dis. 2019. PMID: 31251986
- Trimethylamine N-Oxide: A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function.Canyelles M, Tondo M, Cedó L, Farràs M, Escolà-Gil JC, Blanco-Vaca F. Canyelles M, et al. Int J Mol Sci. 2018 Oct 19;19(10):3228. doi: 10.3390/ijms19103228. Int J Mol Sci. 2018. PMID: 30347638 Free PMC article. Review.
- Trimethylamine-N-oxide: a link between the gut microbiome, bile acid metabolism, and atherosclerosis.Wilson A, McLean C, Kim RB. Wilson A, et al. Curr Opin Lipidol. 2016 Apr;27(2):148-54. doi: 10.1097/MOL.0000000000000274. Curr Opin Lipidol. 2016. PMID: 26959704 Review.
- Trimethylamine N-Oxide Concentration and Blood Pressure in Young Healthy Men and Women: A Replicated Crossover Study.Rowland SN, Heaney LM, Da Boit M, Bailey SJ. Rowland SN, et al. Metabolites. 2023 Jul 24;13(7):876. doi: 10.3390/metabo13070876. Metabolites. 2023. PMID: 37512583 Free PMC article.
- Upregulation of Taurine Biosynthesis and Bile Acid Conjugation with Taurine through FXR in a Mouse Model with Human-like Bile Acid Composition.Miyazaki T, Ueda H, Ikegami T, Honda A. Miyazaki T, et al. Metabolites. 2023 Jul 5;13(7):824. doi: 10.3390/metabo13070824. Metabolites. 2023. PMID: 37512531 Free PMC article.
- Interaction between gut microbiota metabolites and dietary components in lipid metabolism and metabolic diseases.Basnet TB, Gc S, Basnet R, Fatima S, Safdar M, Sehar B, Alsubaie ASR, Zeb F. Basnet TB, et al. Access Microbiol. 2023 Jun 23;5(6):acmi000403. doi: 10.1099/acmi.0.000403. eCollection 2023. Access Microbiol. 2023. PMID: 37424550 Free PMC article. Review.
- Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease.Gabriel CL, Ferguson JF. Gabriel CL, et al. Circ Res. 2023 Jun 9;132(12):1674-1691. doi: 10.1161/CIRCRESAHA.123.322055. Epub 2023 Jun 8. Circ Res. 2023. PMID: 37289901 Review.
- Gut microbiota-derived trimethylamine N-oxide is associated with the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease: a systematic review and dose-response meta-analysis.Li Y, Lu H, Guo J, Zhang M, Zheng H, Liu Y, Liu W. Li Y, et al. Ann Med. 2023 Dec;55(1):2215542. doi: 10.1080/07853890.2023.2215542. Ann Med. 2023. PMID: 37246850 Free PMC article.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Androgens / pharmacology
- Animals
- Atherosclerosis / genetics
- Atherosclerosis / metabolism*
- Atherosclerosis / pathology
- Base Sequence
- Bile Acids and Salts
- Choline / metabolism
- Diet*
- Down-Regulation / drug effects
- Female
- Gene Silencing
- HEK293 Cells
- Humans
- Male
- Methylamines / blood*
- Methylamines / metabolism
- Mice
- Mice, Knockout
- Oxygenases / genetics
- Oxygenases / metabolism
- Polymorphism, Single Nucleotide
- Receptors, Cytoplasmic and Nuclear / genetics
- Receptors, Cytoplasmic and Nuclear / metabolism
- Sex Factors
- Androgens
- Bile Acids and Salts
- Methylamines
- Receptors, Cytoplasmic and Nuclear
- farnesoid X-activated receptor
- Oxygenases
- dimethylaniline monooxygenase (N-oxide forming)
- trimethyloxamine
- trimethylamine
- Choline
- R01 HL094322/HL/NHLBI NIH HHS/United States
- R01 HL103866/HL/NHLBI NIH HHS/United States
- P01 HL028481/HL/NHLBI NIH HHS/United States
- P20 HL113452/HL/NHLBI NIH HHS/United States
- T32GM088088/GM/NIGMS NIH HHS/United States
- HL94322/HL/NHLBI NIH HHS/United States
- HL30568/HL/NHLBI NIH HHS/United States
- R00 HL102223/HL/NHLBI NIH HHS/United States
- P01 HL030568/HL/NHLBI NIH HHS/United States
- K99 HL102223/HL/NHLBI NIH HHS/United States
- K99/R00 HL102223/HL/NHLBI NIH HHS/United States
- HL28481/HL/NHLBI NIH HHS/United States
- HHMI/Howard Hughes Medical Institute/United States
- HL103866/HL/NHLBI NIH HHS/United States
- T32 GM088088/GM/NIGMS NIH HHS/United States
- HL113452/HL/NHLBI NIH HHS/United States
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Research Materials
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 3. Sex and Dietary Choline Regulate…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3771112/bin/nihms431767f3.jpg)
![Figure 4. Gonadal Hormones Regulate Hepatic FMO3…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3771112/bin/nihms431767f4.jpg)
Figure 5. Dietary Cholic Acid Induces Fmo3…
Figure 5. Dietary Cholic Acid Induces Fmo3 Expression and TMAO Levels in Common Inbred Mouse…
Figure 6. FMO3 is an FXR Target…
Figure 6. FMO3 is an FXR Target Gene and FXR Activation Induces FMO3 and Increases…
Figure 7. Natural Genetic Variation of Hepatic…
Figure 7. Natural Genetic Variation of Hepatic FMO3, Plasma TMAO Levels and Atherosclerosis among Common…
- Dioxin-like pollutants increase hepatic flavin containing monooxygenase (FMO3) expression to promote synthesis of the pro-atherogenic nutrient biomarker trimethylamine N-oxide from dietary precursors.Petriello MC, Hoffman JB, Sunkara M, Wahlang B, Perkins JT, Morris AJ, Hennig B. Petriello MC, et al. J Nutr Biochem. 2016 Jul;33:145-53. doi: 10.1016/j.jnutbio.2016.03.016. Epub 2016 Apr 1. J Nutr Biochem. 2016. PMID: 27155921 Free PMC article.
- Genetic Deficiency of Flavin-Containing Monooxygenase 3 ( Fmo3) Protects Against Thrombosis but Has Only a Minor Effect on Plasma Lipid Levels-Brief Report.Shih DM, Zhu W, Schugar RC, Meng Y, Jia X, Miikeda A, Wang Z, Zieger M, Lee R, Graham M, Allayee H, Cantor RM, Mueller C, Brown JM, Hazen SL, Lusis AJ. Shih DM, et al. Arterioscler Thromb Vasc Biol. 2019 Jun;39(6):1045-1054. doi: 10.1161/ATVBAHA.119.312592. Arterioscler Thromb Vasc Biol. 2019. PMID: 31070450 Free PMC article.
- FMO3 and its metabolite TMAO contribute to the formation of gallstones.Chen Y, Weng Z, Liu Q, Shao W, Guo W, Chen C, Jiao L, Wang Q, Lu Q, Sun H, Gu A, Hu H, Jiang Z. Chen Y, et al. Biochim Biophys Acta Mol Basis Dis. 2019 Oct 1;1865(10):2576-2585. doi: 10.1016/j.bbadis.2019.06.016. Epub 2019 Jun 26. Biochim Biophys Acta Mol Basis Dis. 2019. PMID: 31251986
- Trimethylamine N-Oxide: A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function.Canyelles M, Tondo M, Cedó L, Farràs M, Escolà-Gil JC, Blanco-Vaca F. Canyelles M, et al. Int J Mol Sci. 2018 Oct 19;19(10):3228. doi: 10.3390/ijms19103228. Int J Mol Sci. 2018. PMID: 30347638 Free PMC article. Review.
- Trimethylamine-N-oxide: a link between the gut microbiome, bile acid metabolism, and atherosclerosis.Wilson A, McLean C, Kim RB. Wilson A, et al. Curr Opin Lipidol. 2016 Apr;27(2):148-54. doi: 10.1097/MOL.0000000000000274. Curr Opin Lipidol. 2016. PMID: 26959704 Review.
- Trimethylamine N-Oxide Concentration and Blood Pressure in Young Healthy Men and Women: A Replicated Crossover Study.Rowland SN, Heaney LM, Da Boit M, Bailey SJ. Rowland SN, et al. Metabolites. 2023 Jul 24;13(7):876. doi: 10.3390/metabo13070876. Metabolites. 2023. PMID: 37512583 Free PMC article.
- Upregulation of Taurine Biosynthesis and Bile Acid Conjugation with Taurine through FXR in a Mouse Model with Human-like Bile Acid Composition.Miyazaki T, Ueda H, Ikegami T, Honda A. Miyazaki T, et al. Metabolites. 2023 Jul 5;13(7):824. doi: 10.3390/metabo13070824. Metabolites. 2023. PMID: 37512531 Free PMC article.
- Interaction between gut microbiota metabolites and dietary components in lipid metabolism and metabolic diseases.Basnet TB, Gc S, Basnet R, Fatima S, Safdar M, Sehar B, Alsubaie ASR, Zeb F. Basnet TB, et al. Access Microbiol. 2023 Jun 23;5(6):acmi000403. doi: 10.1099/acmi.0.000403. eCollection 2023. Access Microbiol. 2023. PMID: 37424550 Free PMC article. Review.
- Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease.Gabriel CL, Ferguson JF. Gabriel CL, et al. Circ Res. 2023 Jun 9;132(12):1674-1691. doi: 10.1161/CIRCRESAHA.123.322055. Epub 2023 Jun 8. Circ Res. 2023. PMID: 37289901 Review.
- Gut microbiota-derived trimethylamine N-oxide is associated with the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease: a systematic review and dose-response meta-analysis.Li Y, Lu H, Guo J, Zhang M, Zheng H, Liu Y, Liu W. Li Y, et al. Ann Med. 2023 Dec;55(1):2215542. doi: 10.1080/07853890.2023.2215542. Ann Med. 2023. PMID: 37246850 Free PMC article.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Androgens / pharmacology
- Animals
- Atherosclerosis / genetics
- Atherosclerosis / metabolism*
- Atherosclerosis / pathology
- Base Sequence
- Bile Acids and Salts
- Choline / metabolism
- Diet*
- Down-Regulation / drug effects
- Female
- Gene Silencing
- HEK293 Cells
- Humans
- Male
- Methylamines / blood*
- Methylamines / metabolism
- Mice
- Mice, Knockout
- Oxygenases / genetics
- Oxygenases / metabolism
- Polymorphism, Single Nucleotide
- Receptors, Cytoplasmic and Nuclear / genetics
- Receptors, Cytoplasmic and Nuclear / metabolism
- Sex Factors
- Androgens
- Bile Acids and Salts
- Methylamines
- Receptors, Cytoplasmic and Nuclear
- farnesoid X-activated receptor
- Oxygenases
- dimethylaniline monooxygenase (N-oxide forming)
- trimethyloxamine
- trimethylamine
- Choline
- R01 HL094322/HL/NHLBI NIH HHS/United States
- R01 HL103866/HL/NHLBI NIH HHS/United States
- P01 HL028481/HL/NHLBI NIH HHS/United States
- P20 HL113452/HL/NHLBI NIH HHS/United States
- T32GM088088/GM/NIGMS NIH HHS/United States
- HL94322/HL/NHLBI NIH HHS/United States
- HL30568/HL/NHLBI NIH HHS/United States
- R00 HL102223/HL/NHLBI NIH HHS/United States
- P01 HL030568/HL/NHLBI NIH HHS/United States
- K99 HL102223/HL/NHLBI NIH HHS/United States
- K99/R00 HL102223/HL/NHLBI NIH HHS/United States
- HL28481/HL/NHLBI NIH HHS/United States
- HHMI/Howard Hughes Medical Institute/United States
- HL103866/HL/NHLBI NIH HHS/United States
- T32 GM088088/GM/NIGMS NIH HHS/United States
- HL113452/HL/NHLBI NIH HHS/United States
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Research Materials
![Figure 5. Dietary Cholic Acid Induces Fmo3…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3771112/bin/nihms431767f5.jpg)
Figure 6. FMO3 is an FXR Target…
Figure 6. FMO3 is an FXR Target Gene and FXR Activation Induces FMO3 and Increases…
Figure 7. Natural Genetic Variation of Hepatic…
Figure 7. Natural Genetic Variation of Hepatic FMO3, Plasma TMAO Levels and Atherosclerosis among Common…
![Figure 6. FMO3 is an FXR Target…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3771112/bin/nihms431767f6.jpg)
![Figure 7. Natural Genetic Variation of Hepatic…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3771112/bin/nihms431767f7.jpg)
Source: PubMed