Trimethylamine N-oxide – Cardiometabolic Disease Risk Factor or an Osmolyte?

Activity: Talk or presentation types › Oral presentation

Description

Trimethylamine N-oxide (TMAO) is a small molecule generated from intestinal microbiota metabolism of choline and carnitine, therefore plasma levels of TMAO are highly dependent on dietary factors and intestinal microbiota composition. Previously, TMAO was described as an osmolyte that protects cells from osmotic and hydrostatic pressure in deep-sea organisms; however, since 2011 it has been considered a risk factor for cardiometabolic diseases. Despite growing evidence in various patient populations, it is still debated whether TMAO itself exerts detrimental effects or is merely a bystander. The strongest evidence base covers the atherogenic effects of TMAO, namely, aggravated inflammation, stimulation of foam cell formation, and suppression of reverse cholesterol transport. However, the results of preclinical studies are not unanimous, and our data from ex vivo models do not reveal any differences in endothelial function, cardiac function, and infarction size upon acute administration of TMAO. Furthermore, concentration differences in TMAO levels in target tissues must be considered, as we have evidence that TMAO accumulates in the kidneys, resulting in 4- to 10-fold higher concentrations compared to other tissue in rodents after supplementation with TMAO. Subsequently, the kidney mitochondria are also most affected by TMAO, as we observe impaired pyruvate metabolism, leading to increased ROS production. In contrast, in the heart, where TMAO tissue content was lower, we observed preserved mitochondrial energy metabolism and cardiac functionality in experimental model of heart failure. Moreover, data from patients with diabetes indicate that plasma TMAO levels strongly correlate with a marker of kidney tubular damage, which should be an additional exclusion criterion when addressing the validity question of TMAO as a cardiometabolic risk marker. Overall, it seems that the effects of TMAO could depend on the duration of exposure, the composition of the diet, and the disease model; furthermore, the effects can be tissue-specific.. .. .. .
Period29 Mar 2023
Event titleRSU International Research Conference 2023: Knowledge for Use in Practice
Event typeConference
OrganiserRīga Stradiņš University
LocationRiga, LatviaShow on map
Degree of RecognitionInternational

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