A highly sensitive liquid chromatography electrospray ionization mass spectrometry method for quantification of TMA, TMAO and creatinine in mouse urine

Veeravalli, Sunil; Karu, Kersti; Phillips, Ian; Shephard, Elizabeth A.

doi:10.1016/j.mex.2017.09.004

Cited by 15 publications

(11 citation statements)

References 30 publications

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“…Concentrations of TMA, TMAO, and creatinine in urine samples were determined by capillary liquid chromatography electrospray ionization mass spectrometry as described previously ( Veeravalli et al, 2017 ). Production of TMAO was assessed by determining the percentage of total TMA excreted as TMAO, using the following formula: [TMAO/(TMA + TMAO)] × 100 ( Al-Waiz et al, 1989 ).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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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 cholesterol or act as a proatherogenic molecule.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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“…TMA was not quantitated as it typically requires an ethyl bromoacetate derivatization prior to LC/MS analysis, which would have interfered with the detection of other compounds profiled in our analytical panel (e.g. amino acids) ( 68 ). The adult subgroup consisted mainly of females with an unbalanced 1:10 male to female ratio compared with a 1:1 ratio in children.…”

Section: Limitationsmentioning

confidence: 99%

Trimethylamine N-oxide (TMAO) Is not Associated with Cardiometabolic Phenotypes and Inflammatory Markers in Children and Adults

Andraos

Jones

Lange

et al. 2021

Current Developments in Nutrition

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Background Trimethylamine N-oxide (TMAO) is a diet- and microbiome-derived metabolite and a proposed biomarker of adverse cardiometabolic outcomes. TMAO studies have mainly been conducted in individuals with cardiometabolic disease, and studies in population-derived samples are limited. Objective We aimed to investigate the associations between plasma TMAO concentrations and its precursors [carnitine, choline, betaine, and dimethylglycine (DMG)] with metabolic syndrome (MetS) scores, preclinical cardiovascular phenotypes, and inflammatory biomarkers (i.e. high-sensitivity C-reactive protein and serum glycoprotein acetyls) in a population-derived cohort of children and their parents. Methods The concentrations of TMAO and its precursors were quantified using UHPLC coupled with tandem MS (UHPLC/MS-MS) in 1166 children (mean age 11 y ± 0.5 y, 51% female) and 1324 adults (44 y ± 5.1 y, 87% female) participating in The Growing Up in Australia's Child Health CheckPoint Study. We developed multivariable fractional polynomial models to analyze associations between TMAO, its precursors, MetS (adjusted for sex and age), and cardiovascular phenotypes (adjusted for sex, age, BMI, household income, and the urinary albumin to creatinine ratio). Pearson's correlations were computed to identify associations between TMAO, its precursors, and inflammatory biomarkers. Results The concentrations of TMAO precursors, but not TMAO itself, were associated with MetS, cardiovascular phenotypes, and inflammatory biomarkers in children and adults. Conclusions TMAO precursors, but not TMAO itself, were associated with adverse cardiometabolic and inflammatory phenotypes in children and adults. TMAO precursor concentrations may better reflect cardiovascular health and inflammatory status within the wider population. Replication in other population settings and mechanistic studies are warranted.

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“…It has been recently described a new method to measure TMAO in urine combining TMA derivation with ethyl-bromoacetate and liquid chromatography with single ion monitoring (LC-SIM) [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target

et al. 2018

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Trimethylamine N-oxide (TMAO) is a molecule generated from choline, betaine, and carnitine via gut microbial metabolism. The plasma level of TMAO is determined by several factors including diet, gut microbial flora, drug administration and liver flavin monooxygenase activity. In humans, recent clinical studies evidence a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events. A direct correlation between increased TMAO levels and neurological disorders has been also hypothesized. Several therapeutic strategies are being explored to reduce TMAO levels, including use of oral broad spectrum antibiotics, promoting the growth of bacteria that use TMAO as substrate and the development of target-specific molecules. Despite the accumulating evidence, it is questioned whether TMAO is the mediator of a bystander in the disease process. Thus, it is important to undertake studies to establish the role of TMAO in human health and disease. In this article, we reviewed dietary sources and metabolic pathways of TMAO, as well as screened the studies suggesting possible involvement of TMAO in the etiology of cardiovascular and neurological disorders, underlying the importance of TMAO mediating inflammatory processes. Finally, the potential utility of TMAO as therapeutic target is also analyzed.

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A highly sensitive liquid chromatography electrospray ionization mass spectrometry method for quantification of TMA, TMAO and creatinine in mouse urine

Abstract: Graphical abstract

Cited by 15 publications

References 30 publications

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

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

Trimethylamine N-oxide (TMAO) Is not Associated with Cardiometabolic Phenotypes and Inflammatory Markers in Children and Adults

Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target

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