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Abstract #0036

In vivo 2H-MR spectroscopy of trimethylamine metabolism in the liver by the hepatic enzyme FMO3

Hadar Dessau1, Talia Harris2, Hyla Allouche-Arnon1, and Amnon Bar-Shir1
1Molecular Chemistry and Materials Science, Weizmann Institute of Science, Rehovot, Israel, 2Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel

Synopsis

Keywords: Deuterium, Metabolism, Metabolic pathway; Trimethyamine; Trimethylamine oxide;2D-CSI;DMI;2H-MRS;metabolic imaging;FMO3;Liver;disease;Mice

Motivation: The metabolite trimethylamine oxide (TMAO) is linked to multiple diseases, and there is a need for a clinically translatable tool to monitor its longitudinal formation in vivo.

Goal(s): To develop an approach to monitor quantitatively the formation of TMAO in a non-invasive manner in deep tissues of live subjects.

Approach: In vivo deuterium metabolic spectroscopy and imaging were applied to monitor and quantify the conversion of deuterium-labeled trimethylamine (TMA-d9) in the liver.

Results: The conversion of TMA-d9 to TMAO-d9 was monitored by 2H-MRS and was found to be correlated with FMO3 expression levels that are significantly higher in female compared to male mice.

Impact: The ability to monitor the TMA-d9-to-TMAO-d9 metabolism will allow us to follow, for the first time longitudinally and non-invasively, the role of TMAO in the onset and progression of multiple diseases ranging from cancer to cardiovascular disease.

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