Journal article

Plasma levels of trimethylamine-N-oxide can be increased with 'healthy' and 'unhealthy' diets and do not correlate with the extent of atherosclerosis but with plaque instability

Yen Chin Koay, Yung-Chih Chen, Jibran A Wali, Alison WS Luk, Mengbo Li, Hemavarni Doma, Rosa Reimark, Maria TK Zaldivia, Habteab T Habtom, Ashley E Franks, Gabrielle Fusco-Allison, Jean Yang, Andrew Holmes, Stephen J Simpson, Karlheinz Peter, John F O'Sullivan



AIMS: The microbiome-derived metabolite trimethylamine-N-oxide (TMAO) has attracted major interest and controversy both as a diagnostic biomarker and therapeutic target in atherothrombosis. METHODS AND RESULTS: Plasma TMAO increased in mice on 'unhealthy' high-choline diets and notably also on 'healthy' high-fibre diets. Interestingly, TMAO was found to be generated by direct oxidation in the gut in addition to oxidation by hepatic flavin-monooxygenases. Unexpectedly, two well-accepted mouse models of atherosclerosis, ApoE-/- and Ldlr-/- mice, which reflect the development of stable atherosclerosis, showed no association of TMAO with the extent of atherosclerosis. This finding was validated ..

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Awarded by Sydney Medical School Foundation Chapman Fellowship

Awarded by NSW Clinician-Scientist Award

Awarded by Future Leader Fellowship

Awarded by Boston University

Awarded by NHLBI

Awarded by National Institutes of Health

Funding Acknowledgements

This work was supported by the Heart Research Institute (J.F.O.S. and Y.C.K.), Sydney Medical School Foundation Chapman Fellowship (J.F.O.S.), NSWHealth Early-Mid Career Fellowship (J.F.O.S., DOH1003) and by NSW Clinician-Scientist Award (J.F.O.S., DOH1006). K.P. was supported by a National Health and Medical Research Council Principle Research Fellowship. Y.C.C. was supported by a Future Leader Fellowship (Reference No. 102068) from the National Heart Foundation of Australia. Framingham data: The Framingham Heart Study (FHS) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195 and HHSN268201500001I). This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or NHLBI. Funding for SHARe Affymetrix genotyping was provided by NHLBI Contract N02-HL-64278. SHARe Illumina genotyping was provided under an agreement between Illumina and Boston University. Funding for Affymetrix genotyping of the FHS Omni cohorts was provided by Intramural NHLBI funds from Andrew D. Johnson and Christopher J. O'Donnell. Funding support for the Framingham Targeted and Untargeted Metabolomics-HILIC-Installment 1 dataset was provided by Massachusetts General Hospital Departmental funding. Funding support for the Framingham Metabolomics (HILIC-Installment 1, 2, and 3) datasets, Framingham Central Metabolomics-HILIC-Installment 1 and 2, and Lipid Platform-Installment 1 and 2, were provided by National Institutes of Health (R01 DK081572).