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

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.