Effect of Flavin-Containing Monooxygenase Genotype, Mouse Strain, and Gender on Trimethylamine N-oxide Production, Plasma Cholesterol Concentration, and an Index of Atherosclerosis.

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Sunil VeeravalliElizabeth A Shephard

Abstract

The objectives of the study were to determine the contribution, in mice, of members of the flavin-containing monooxygenase (FMO) family to the production of trimethylamine (TMA) N-oxide (TMAO), a potential proatherogenic molecule, and whether under normal dietary conditions differences in TMAO production were associated with changes in plasma cholesterol concentration or with an index of atherosclerosis (Als). Concentrations of urinary TMA and TMAO and plasma cholesterol were measured in 10-week-old male and female C57BL/6J and CD-1 mice and in mouse lines deficient in various Fmo genes (Fmo1-/- , 2-/- , 4-/- , and Fmo5-/- ). In female mice most TMA N-oxygenation was catalyzed by FMO3, but in both genders 11%-12% of TMA was converted to TMAO by FMO1. Gender-, Fmo genotype-, and strain-related differences in TMAO production were accompanied by opposite effects on plasma cholesterol concentration. Plasma cholesterol was negatively, but weakly, correlated with TMAO production and urinary TMAO concentration. Fmo genotype had no effect on Als. There was no correlation between Als and either TMAO production or urinary TMAO concentration. Our results indicate that under normal dietary conditions TMAO does not increase plasma cholester...Continue Reading

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Citations

Jun 20, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Cassandra JohnsonJason R Stubbs
Jul 19, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Ian R Phillips, Elizabeth A Shephard
Mar 12, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sunil VeeravalliElizabeth A Shephard
Jul 29, 2020·Nutrition Research Reviews·Saba NaghipourJohn P Headrick
May 13, 2020·Nutrients·Christopher PapandreouAouatef Bellamine
Sep 9, 2020·Scientific Reports·Yu HasegawaCarolyn M Slupsky
Apr 21, 2020·Frontiers in Pharmacology·Remy VillettePhilippe Lesnik
Sep 25, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mario BonominiArduino Arduini
Dec 25, 2019·Nature Structural & Molecular Biology·Callum R NicollAndrea Mattevi
Feb 13, 2021·The Journal of Nutritional Biochemistry·Lisard Iglesias-CarresAndrew P Neilson
Mar 2, 2021·Frontiers in Cell and Developmental Biology·Shijiao HuangScott F Leiser
Jun 2, 2018·Chemical Research in Toxicology·Jennifer SchneiderBernd Clement

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BETA
gene knockout

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geNorm

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