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Carnitine tmao

Jia Liu, Mingming Zhao, Juntuo Zhou, Changjie Liu, Lemin Zheng, Yuxin Yin
Trimethylamine-N-oxide (TMAO) is a metabolite generated from choline, betaine and carnitine in a gut microbiota-dependent way. This molecule is associated with development of atherosclerosis and cardiovascular events. A sensitive liquid chromatographic electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated for the simultaneous determination of TMAO related molecules including TMAO, betaine, choline, and carnitine in mouse plasma. Analytes are extracted after protein precipitation by methanol and subjected to LC-ESI-MS/MS without preliminary derivatization...
November 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Amit Sharma, Jyoti Chhibber-Goel, Varsha Singhal, Neeraj Parakh, Balram Bhargava
Trimethylamine-N-oxide (TMAO) is a low molecular weight metabolite whose production is dependent on metabolism of its precursors choline, carnitine, creatinine, betaine or lecithin by host gut microbes resulting in the synthesis of trimethylamine (TMA) and subsequent oxidation to TMAO via the hepatic flavin monooxygenase (FMO) enzyme or bacterial Trimethylamine Monooxygenase (TMM). TMAO is associated with microbial dysbiosis and it is being studied for its linkage with cardiovascular disorders. In addition, dysregulated levels of TMAO has been linked with renal diseases, neurological disorders, and cancer...
August 30, 2016: Current Medicinal Chemistry
Clara E Cho, Siraphat Taesuwan, Olga V Malysheva, Erica Bender, Nathan F Tulchinsky, Jian Yan, Jessica L Sutter, Marie A Caudill
SCOPE: Trimethylamine-N-oxide (TMAO), a metabolite linked to the gut microbiota, is associated with excess risk of heart disease. We hypothesized that (i) TMAO response to animal source foods would vary among healthy men and (ii) this response would be modified by their gut microbiome. METHODS AND RESULTS: A crossover feeding trial in healthy young men (n = 40) was conducted with meals containing TMAO (fish), its dietary precursors, choline (eggs) and carnitine (beef), and a fruit control...
July 5, 2016: Molecular Nutrition & Food Research
Reynold Spector
At present, the guideline approach to the medical treatment and prevention of atherosclerotic cardiovascular disease (ASCVD) is to classify patients by risk and treat the known risk factors (contributory causes), e.g., hypertension, diabetes, obesity, smoking, and poor diet, as appropriate. All high-risk patients should receive statins. This approach has had substantial success but ASCVD still remains the number one cause of death in the United States. Until recently, the underlying cause of ASCVD remained unknown, although a potential dietary cause was suggested by the fact that vegetarians, especially vegans, have a much lower incidence of ASCVD than animal flesh eaters...
July 2016: Journal of Pharmacology and Experimental Therapeutics
Michael C Petriello, Jessie B Hoffman, Manjula Sunkara, Banrida Wahlang, Jordan T Perkins, Andrew J Morris, Bernhard Hennig
The etiology of cardiovascular disease (CVD) is impacted by multiple modifiable and non-modifiable risk factors including dietary choices, genetic predisposition, and environmental exposures. However, mechanisms linking diet, exposure to pollutants, and CVD risk are largely unclear. Recent studies identified a strong link between plasma levels of nutrient-derived Trimethylamine N-oxide (TMAO) and coronary artery disease. Dietary precursors of TMAO include carnitine and phosphatidylcholine, which are abundant in animal-derived foods...
July 2016: Journal of Nutritional Biochemistry
M Dambrova, G Latkovskis, J Kuka, I Strele, I Konrade, S Grinberga, D Hartmane, O Pugovics, A Erglis, E Liepinsh
Recent studies have revealed strong associations between systemic trimethylamine N-oxide (TMAO) levels, atherosclerosis and cardiovascular risk. In addition, plasma L-carnitine levels in patients with high TMAO concentrations predicted an increased risk for cardiovascular disease and incident major adverse cardiac events. The aim of the present study was to investigate the relation between TMAO and L-carnitine plasma levels and diabetes. Blood plasma samples were collected from 12 and 20 weeks old db/db mice and patients undergoing percutaneous coronary intervention...
April 2016: Experimental and Clinical Endocrinology & Diabetes
I Jane Cox, Abil E Aliev, Mary Me Crossey, Mahvish Dawood, Mamun Al-Mahtab, Sheikh M Akbar, Salimur Rahman, Antonio Riva, Roger Williams, Simon D Taylor-Robinson
AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma (HCC) patients compared to cirrhosis patients and controls. METHODS: Urine samples from 42 Bangladeshi patients with HCC (39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance (NMR) spectroscopy...
April 28, 2016: World Journal of Gastroenterology: WJG
Richard B Kim, Bridget L Morse, Ognjenka Djurdjev, Mila Tang, Norman Muirhead, Brendan Barrett, Daniel T Holmes, Francois Madore, Catherine M Clase, Claudio Rigatto, Adeera Levin
Cardiovascular disease is more common in patients with chronic kidney disease (CKD), and traditional risk factors do not adequately predict those at risk for cardiovascular (CV) events. Recent evidence suggests elevated trimethylamine N-oxide (TMAO), created by gut microflora from dietary L-carnitine and choline, is associated with CV events. We investigated the relationship of TMAO levels in patients with stages 3b and 4 CKD to ischemic CV events using the CanPREDDICT cohort, a Canada-wide observational study with prospective 3-year follow-up of adjudicated CV events...
May 2016: Kidney International
Marius Trøseid, Johannes R Hov, Torunn Kristin Nestvold, Hanne Thoresen, Rolf K Berge, Asbjørn Svardal, Knut Tore Lappegård
BACKGROUND: Trimethylamine-N-oxide (TMAO) is formed in the liver from trimethylamine (TMA), a product exclusively generated by the gut microbiota from dietary phosphatidylcholine and carnitine. An alternative pathway of TMAO formation from carnitine is via the microbiota-dependent intermediate γ-butyrobetaine (γBB). Elevated TMAO levels are associated with cardiovascular disease (CVD), but little is known about TMAO in obesity. Given the proposed contribution of microbiota alterations in obesity and type 2 diabetes (T2D), we investigated the potential impact of obesity, lifestyle-induced weight loss, and bariatric surgery on plasma levels of TMAO, its microbiota-dependent intermediate γBB, and its diet-dependent precursors carnitine and choline...
May 2016: Metabolic Syndrome and related Disorders
Hanane Kadar, Justine Dubus, Jérémie Dutot, Lyamine Hedjazi, Suman Srinivasa, Kathleen V Fitch, Steven K Grinspoon, Jeremy K Nicholson, Marc-Emmanuel Dumas, Dominique Gauguier
Methylamines are biologically-active metabolites present in serum and urine samples, which play complex roles in metabolic diseases. Methylamines can be detected by proton nuclear magnetic resonance (NMR), but specific methods remain to be developed for their routine assay in human serum in clinical settings. Here we developed and validated a novel reliable "methylamine panel" method for simultaneous quantitative analysis of trimethylamine (TMA), its major detoxification metabolite trimethylamine-N-oxide (TMAO), and precursors choline, betaine and l-carnitine in human serum using Ultra Performance Liquid Chromatography (UPLC) coupled to High Resolution Mass Spectrometry (HRMS)...
May 1, 2016: Archives of Biochemistry and Biophysics
Marcus J Miller, Bret L Bostwick, Adam D Kennedy, Taraka R Donti, Qin Sun, V Reid Sutton, Sarah H Elsea
Recent studies have implicated trimethylamine N-oxide (TMAO) in atherosclerosis, raising concern about L-carnitine, a common supplement for patients with inborn errors of metabolism (IEMs) and a TMAO precursor metabolized, in part, by intestinal microbes. Dietary meat restriction attenuates carnitine-to-TMAO conversion, suggesting that TMAO production may not occur in meat-restricted individuals taking supplemental L-carnitine, but this has not been tested. Here, we mine a metabolomic dataset to assess TMAO levels in patients with diverse IEMs, including organic acidemias...
March 3, 2016: JIMD Reports
Mette Schmedes, Eli Kristin Aadland, Ulrik Kraemer Sundekilde, Hélène Jacques, Charles Lavigne, Ingvild Eide Graff, Øyvin Eng, Asle Holthe, Gunnar Mellgren, Jette Feveile Young, Hanne Christine Bertram, Bjørn Liaset, Morten Rahr Clausen
SCOPE: Proteins constitute an important part of the human diet, but understanding of the effects of different dietary protein sources on human metabolism is sparse. We aimed to elucidate diet-induced metabolic changes through untargeted urinary metabolomics after four weeks of intervention with lean-seafood or nonseafood diets. It is shown that lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects...
July 2016: Molecular Nutrition & Food Research
Karolina Skagen, Marius Trøseid, Thor Ueland, Sverre Holm, Azhar Abbas, Ida Gregersen, Martin Kummen, Vigdis Bjerkeli, Frode Reier-Nilsen, David Russell, Asbjørn Svardal, Tom Hemming Karlsen, Pål Aukrust, Rolf K Berge, Johannes E R Hov, Bente Halvorsen, Mona Skjelland
BACKGROUND AND PURPOSE: γ-butyrobetaine (γBB) is a metabolite from dietary Carnitine, involved in the gut microbiota-dependent conversion from Carnitine to the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO). Orally ingested γBB has a pro-atherogenic effect in experimental studies, but γBB has not been studied in relation to atherosclerosis in humans. The aim of this study was to evaluate associations between serum levels of γBB, TMAO and their common precursors Carnitine and trimethyllysine (TML) and carotid atherosclerosis and adverse outcome...
April 2016: Atherosclerosis
Zeneng Wang, Adam B Roberts, Jennifer A Buffa, Bruce S Levison, Weifei Zhu, Elin Org, Xiaodong Gu, Ying Huang, Maryam Zamanian-Daryoush, Miranda K Culley, Anthony J DiDonato, Xiaoming Fu, Jennie E Hazen, Daniel Krajcik, Joseph A DiDonato, Aldons J Lusis, Stanley L Hazen
Trimethylamine (TMA) N-oxide (TMAO), a gut-microbiota-dependent metabolite, both enhances atherosclerosis in animal models and is associated with cardiovascular risks in clinical studies. Here, we investigate the impact of targeted inhibition of the first step in TMAO generation, commensal microbial TMA production, on diet-induced atherosclerosis. A structural analog of choline, 3,3-dimethyl-1-butanol (DMB), is shown to non-lethally inhibit TMA formation from cultured microbes, to inhibit distinct microbial TMA lyases, and to both inhibit TMA production from physiologic polymicrobial cultures (e...
December 17, 2015: Cell
Jia Yin, Shuo-Xi Liao, Yan He, Shan Wang, Geng-Hong Xia, Fei-Tong Liu, Jia-Jia Zhu, Chao You, Qiong Chen, Liang Zhou, Su-Yue Pan, Hong-Wei Zhou
BACKGROUND: Gut microbiota has been suggested to play a role in almost all major diseases including cardio- and cerebrovascular diseases. A possible mechanism is the transformation of dietary choline and l-carnitine into trimethylamine by gut bacteria. This metabolite is further oxidized into trimethylamine-N-oxide (TMAO) in liver and promotes atherogenesis. Nevertheless, little is known about gut microbial diversity and blood TMAO levels in stroke patients. METHODS AND RESULTS: We performed a case-control study of patients with large-artery atherosclerotic ischemic stroke and transient ischemic attack...
November 2015: Journal of the American Heart Association
Heidi L Collins, Denise Drazul-Schrader, Anthony C Sulpizio, Paul D Koster, Yuping Williamson, Steven J Adelman, Kevin Owen, Toran Sanli, Aouatef Bellamine
OBJECTIVE: Dietary l-carnitine can be metabolized by intestinal microbiota to trimethylamine, which is absorbed by the gut and further oxidized to trimethylamine N-oxide (TMAO) in the liver. TMAO plasma levels have been associated with atherosclerosis development in ApoE(-/-) mice. To better understand the mechanisms behind this association, we conducted in vitro and in vivo studies looking at the effect of TMAO on different steps of atherosclerotic disease progression. METHODS: J774 mouse macrophage cells were used to evaluate the effect of TMAO on foam cell formation...
January 2016: Atherosclerosis
Daniel M Mueller, Martina Allenspach, Alaa Othman, Christoph H Saely, Axel Muendlein, Alexander Vonbank, Heinz Drexel, Arnold von Eckardstein
BACKGROUND: After ingestion of phosphatidylcholine, l-carnitine or betaine, trimethylamine-N-oxide (TMAO) is formed by gut microbiota and liver enzymes. Elevated TMAO plasma levels were associated with increased cardiovascular risk and other diseases. Also betaine and choline itself were recently associated with increased cardiovascular risk. METHODS: A newly developed LC-HRMS method was applied to measure the plasma concentrations of TMAO, betaine and choline in a cohort of 339 patients undergoing coronary angiography for the evaluation of suspected coronary artery disease...
December 2015: Atherosclerosis
Nabil E Boutagy, Andrew P Neilson, Kristin L Osterberg, Andrew T Smithson, Tessa R Englund, Brenda M Davy, Matthew W Hulver, Kevin P Davy
OBJECTIVE: The objective of this study was to test the hypothesis that the multi-strain probiotic VSL#3 would attenuate the increase in fasting plasma concentrations of trimethylamine-N-oxide (TMAO) following a high-fat diet. METHODS: Nineteen healthy, non-obese males (18-30 years) participated in the present study. Following a 2-week eucaloric control diet, subjects were randomized to either VSL#3 (900 billion live bacteria) or placebo (cornstarch) during the consumption of a hypercaloric (+1,000 kcal day(-1) ), high-fat diet (55% fat) for 4 weeks...
December 2015: Obesity
Guro F Giskeødegård, Sarah K Davies, Victoria L Revell, Hector Keun, Debra J Skene
Understanding how metabolite levels change over the 24 hour day is of crucial importance for clinical and epidemiological studies. Additionally, the association between sleep deprivation and metabolic disorders such as diabetes and obesity requires investigation into the links between sleep and metabolism. Here, we characterise time-of-day variation and the effects of sleep deprivation on urinary metabolite profiles. Healthy male participants (n = 15) completed an in-laboratory study comprising one 24 h sleep/wake cycle prior to 24 h of continual wakefulness under highly controlled environmental conditions...
2015: Scientific Reports
Bodil Bjørndal, Marie S Ramsvik, Carine Lindquist, Jan E Nordrehaug, Inge Bruheim, Asbjørn Svardal, Ottar Nygård, Rolf K Berge
Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks...
September 2015: Marine Drugs
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