Simultaneous determination of trimethylamine N -oxide, choline, betaine by UPLC–MS/MS in human plasma: An application in acute stroke patients

Yu, Wei-Bang; Xu, Chunhai; Li, Guo-min; Hong, Weipeng; Zhou, Ziyi; Xiao, Can-xing; Zhao, Yuanqi; Cai, Yefeng; Huang, Min; Jin, Jing

doi:10.1016/j.jpba.2018.01.049

Cited by 28 publications

(21 citation statements)

References 24 publications

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“…Chromatographic separation was performed with a Luna HILIC column (150 × 3 mm, 5 µm particles) in combination with a guard column (HILIC), both supplied by Phenomenex (Torrance, CA, USA). The intra-assay coefficients of variations (CV) was <5.5%, as already widely reported in our previous studies [32,33,34,35,36]. FLI was calculated with the formula: (FLI = eL/(1 + eL) × 100, L = 0.953 × loge triglycerides + 0.139 BMI + 0.718 × logeγGT + 0.053 × WC−15.745).…”

Section: Methodsmentioning

confidence: 66%

“…The quantification of plasma TMAO concentrations was performed using the method described by Beale and Airs [30] and reported in our previous study [10,31]. Briefly, serum proteins were precipitated with methanol (serum:methanol, 1:2, v / v ); samples were vortex-mixed for 2 min, centrifuged at 14,000 g for 10 min (4 °C) [32], and supernatants were collected and analyzed by the High Performance Liquid Chromatography–Mass Spectrometry (HPLC/MS) method. Both HPLC/MS conditions and method optimization were performed in accordance with Beale and Airs [30].…”

Section: Methodsmentioning

confidence: 99%

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A New Light on Vitamin D in Obesity: A Novel Association with Trimethylamine-N-Oxide (TMAO)

Barrea¹,

Muscogiuri²,

Annunziata

et al. 2019

Nutrients

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Vitamin D deficiency and obesity are two public health problems extensively exacerbated over the last years. Among the several mechanisms proposed to account for the complex interplay between vitamin D and obesity, one that has gained particular attention is related to the emerging role of obesity-related changes in gut microbiota and gut-derived metabolites, such as Trimethylamine-N-oxide (TMAO). Vitamin D deficiency and high circulating TMAO levels are associated with body weight and the severity of non-alcoholic fatty liver disease (NAFLD). Considering the link of obesity with vitamin D on the one hand and obesity with TMAO on the other hand, and the central role of the liver in both the vitamin D and TMAO metabolism, the aim of this cross-sectional observational study was first, to confirm the possible inverse association between vitamin D and TMAO across different body mass index (BMI) classes and second, to investigate if this association could be influenced by the presence of NAFLD. One hundred and four adult subjects (50 males and 54 females; 35.38 ± 7.49 years) were enrolled. The fatty liver index (FLI) was used as a proxy for the diagnosis of NAFLD. Vitamin D deficiency was found in 65 participants (62.5%), while 33 subjects (31.7%) had insufficient levels, and the remaining subjects had sufficient levels of vitamin D. Subjects with both vitamin D deficiency and FLI-NAFLD had the highest TMAO levels (p < 0.001). By stratifying the sample population according to the BMI classes, vitamin D levels decreased significantly along with the increase of plasma TMAO concentrations, with the lowest vitamin D levels and highest TMAO, respectively, in class III obesity. Vitamin D levels showed significant opposite associations with circulating levels of TMAO (r = −0.588, p < 0.001), but this association was no longer significant after the adjustment for FLI values. The highest values of TMAO were significantly associated with the severity of obesity (OR 7.92; p < 0.001), deficiency of vitamin D (OR 1.62; p < 0.001), and FLI-NAFLD (OR 3.79; p < 0.001). The most sensitive and specific cut-off for vitamin D to predict the circulating levels of TMAO was ≤19.83 ng/mL (p < 0.001). In conclusion, our study suggests that high TMAO levels are associated with vitamin D deficiency and NAFLD. Further studies are required to investigate if there is a causality link or whether all of them are simply the consequence of obesity.

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Section: Methodsmentioning

confidence: 66%

Section: Methodsmentioning

confidence: 99%

A New Light on Vitamin D in Obesity: A Novel Association with Trimethylamine-N-Oxide (TMAO)

Barrea¹,

Muscogiuri²,

Annunziata

et al. 2019

Nutrients

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show abstract

“…The quantification of circulating TMAO levels has been performed using the method described by Beale and Airs [30], and reported in our previous study [4], with slight modifications. Briefly, serum proteins were precipitated with methanol (serum:methanol, 1:2, v / v ); samples were vortex-mixed for 2 min, centrifuged at 14,000 g for 10 min (4 °C) [31] and supernatants were collected and analyzed by High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) method. Both HPLC-MS conditions and method optimization were performed in accordance with Beale and Airs [30].…”

Section: Methodsmentioning

confidence: 99%

Trimethylamine-N-oxide (TMAO) as Novel Potential Biomarker of Early Predictors of Metabolic Syndrome

et al. 2018

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There is a mechanistic link between the gut-derived metabolite trimethylamine-N-oxide (TMAO) and obesity-related diseases, suggesting that the TMAO pathway may also be linked to the pathogenesis of obesity. The Visceral Adiposity Index (VAI), a gender-specific indicator of adipose dysfunction, and the Fatty Liver Index (FLI), a predictor of non-alcoholic fatty liver disease (NAFLD), are early predictors of metabolic syndrome (MetS). In this cross-sectional observational study, we investigated TMAO levels in adults stratified according to Body Mass Index (BMI) and the association of TMAO with VAI and FLI. One hundred and thirty-seven adult subjects (59 males; 21–56 years) were enrolled. TMAO levels were detected using HPLC/MS analysis. Homeostatic Model Assessment of Insulin Resistance (HoMA-IR), VAI and FLI were included as cardio-metabolic indices. TMAO levels increased along with BMI and were positively associated with VAI and FLI, independently, on common potential covariates. The most sensitive and specific cut-offs for circulating levels of TMAO to predict the presence of NAFLD-FLI and MetS were ≥8.02 µM and ≥8.74 µM, respectively. These findings allow us to hypothesize a role of TMAO as an early biomarker of adipose dysfunction and NAFLD-FLI in all borderline conditions in which overt MetS is not present, and suggest that a specific cut-off of TMAO might help in identifying subjects at high risk of NAFLD.

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“…Briefly, 160 µL of methanol was added to 80 µL of plasma, in order to precipitate serum proteins. The mixture was vortex-mixed for 2 min, centrifuged at 12,000 rpm for 10 min (4 °C) [32,33,34], and the supernatants were used for the HPLC-MS analysis. The HPLC/MS system used and method conditions are reported in the Supplementary Materials.…”

Section: Methodsmentioning

confidence: 99%

Effects of Grape Pomace Polyphenolic Extract (Taurisolo®) in Reducing TMAO Serum Levels in Humans: Preliminary Results from a Randomized, Placebo-Controlled, Cross-Over Study

et al. 2019

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Trimethylamine N-oxide (TMAO) is considered a novel risk factor for cardiovascular diseases. Several studies demonstrated that polyphenols are able to inhibit the growth of TMA-producing bacterial strains, and resveratrol (RSV) reduced TMAO levels in mice. In the present study, we evaluated the TMAO-reducing effect of a novel nutraceutical formulation containing grape pomace extract in humans (Taurisolo®). The Taurisolo® polyphenol content was evaluated by a High Performance Liquid Chromatography-diode-array detector (HPLC-DAD) method, and RSV was monitored as an indicative marker. After in vitro GI digestion, intestinal bioaccessibility of RSV was 92.3%. A randomized, placebo-controlled, cross-over trial was carried out to evaluate the TMAO-reducing effect of Taurisolo®. In acute, the maximum levels of RSV were detected both in serum and whole blood 60 min after the administration of Taurisolo®; in chronic, a significant increase of RSV was detected in serum after the 4-week treatment. After 4 weeks, the levels of TMAO were significantly decreased in the treatment group compared to placebo (63.6% vs. 0.54%, respectively, P < 0.0001). In conclusion, our data show that Taurisolo® may represent a novel and useful natural remedy to reduce prognostic markers for incident cardiovascular events. Undoubtedly, further in vitro and in vivo studies need to be performed in order to elucidate possible mechanisms of action and corroborate our preliminary results.

show abstract

Simultaneous determination of trimethylamine N -oxide, choline, betaine by UPLC–MS/MS in human plasma: An application in acute stroke patients

Cited by 28 publications

References 24 publications

A New Light on Vitamin D in Obesity: A Novel Association with Trimethylamine-N-Oxide (TMAO)

A New Light on Vitamin D in Obesity: A Novel Association with Trimethylamine-N-Oxide (TMAO)

Trimethylamine-N-oxide (TMAO) as Novel Potential Biomarker of Early Predictors of Metabolic Syndrome

Effects of Grape Pomace Polyphenolic Extract (Taurisolo®) in Reducing TMAO Serum Levels in Humans: Preliminary Results from a Randomized, Placebo-Controlled, Cross-Over Study

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