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https://www.readbyqxmd.com/read/28645263/microbiota-dependent-metabolite-and-cardiovascular-disease-marker-trimethylamine-n-oxide-tmao-is-associated-with-monocyte-activation-but-not-platelet-function-in-untreated-hiv-infection
#1
Judith M Haissman, Anna K Haugaard, Sisse R Ostrowski, Rolf K Berge, Johannes R Hov, Marius Trøseid, Susanne D Nielsen
BACKGROUND: HIV infection is associated with increased risk of cardiovascular disease beyond that explained by traditional risk factors. Altered gut microbiota, microbial translocation, and immune activation have been proposed as potential triggers. The microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) predicts myocardial infarction (MI) in the general population and has recently been shown to induce platelet hyperreactivity. In the present study, we investigated if TMAO was associated with platelet function, microbial translocation, and immune activation in both untreated and combination anti-retroviral therapy (cART) HIV infection...
June 23, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28641532/trimethylamine-n-oxide-tmao-as-a-new-potential-therapeutic-target-for-insulin-resistance-and-cancer
#2
Jens Oellgaard, Signe Abitz Winther, Tobias Schmidt Hansen, Peter Rossing, Bernt Johan von Scholten
BACKGROUND: The intake of animal products in food has been associated with both the development of insulin resistance and gastrointestinal cancers (GIC). Through the digestion of animal protein and other constituents of animal products, the commensal bacteria in the gut (the gut microbiota) forms metabolites that can contribute to the development of both insulin resistance and cancer. Trimethylamine-N-Oxide (TMAO) is such a molecule and has recently drawn a lot of attention as it may be a risk factor for - and a link between - the gut microbiota and cardiovascular and renal disease...
June 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28636934/the-tmao-producing-enzyme-flavin-containing-monooxygenase-3-regulates-obesity-and-the-beiging-of-white-adipose-tissue
#3
Rebecca C Schugar, Diana M Shih, Manya Warrier, Robert N Helsley, Amy Burrows, Daniel Ferguson, Amanda L Brown, Anthony D Gromovsky, Markus Heine, Arunachal Chatterjee, Lin Li, Xinmin S Li, Zeneng Wang, Belinda Willard, YongHong Meng, Hanjun Kim, Nam Che, Calvin Pan, Richard G Lee, Rosanne M Crooke, Mark J Graham, Richard E Morton, Carl D Langefeld, Swapan K Das, Lawrence L Rudel, Nizar Zein, Arthur J McCullough, Srinivasan Dasarathy, W H Wilson Tang, Bernadette O Erokwu, Chris A Flask, Markku Laakso, Mete Civelek, Sathyamangla V Naga Prasad, Joerg Heeren, Aldons J Lusis, Stanley L Hazen, J Mark Brown
Emerging evidence suggests that microbes resident in the human intestine represent a key environmental factor contributing to obesity-associated disorders. Here, we demonstrate that the gut microbiota-initiated trimethylamine N-oxide (TMAO)-generating pathway is linked to obesity and energy metabolism. In multiple clinical cohorts, systemic levels of TMAO were observed to strongly associate with type 2 diabetes. In addition, circulating TMAO levels were associated with obesity traits in the different inbred strains represented in the Hybrid Mouse Diversity Panel...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28629999/trimethylamine-n-oxide-prime-nlrp3-inflammasome-via-inhibiting-atg16l1-induced-autophagy-in-colonic-epithelial-cells
#4
Chaochi Yue, Xiangdong Yang, Jun Li, Xiaochao Chen, Xiangdong Zhao, Ye Chen, Yong Wen
Recently, the intricate relationship between Trimethylamine N-oxide (TMAO) and inflammatory bowel disease (IBD) is of growing interest. The NLRP3 inflammasome plays crucial roles in gut homeostasis and determining the severity of inflammation in IBD, however, the precise roles of the NLRP3 inflammasome in IBD are still debated. ATG16L1 mediates the cellular degradative process of autophagy and is considered a critical regulator of inflammation based on its genetic association with IBD. Whether TMAO prime NLRP3 inflammasome via ATG16L1-induced autophagy remains unclear...
June 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28627164/thermodynamic-and-structural-adaptation-differences-between-the-mesophilic-and-psychrophilic-lactate-dehydrogenases
#5
Sergei Khrapunov, Eric P Chang, Robert Callender
The thermodynamics of substrate binding and enzymatic activity of a glycolytic enzyme, lactate dehydrogenase (LDH), from both porcine heart, phLDH (Sus scrofa; a mesophile), and from mackerel icefish, cgLDH (Chamapsocephalus gunnari; a psychrophile), were investigated. Using a novel and quite sensitive fluorescence assay which can distinguish protein conformational changes close and distal from the substrate binding pocket, a reversible global protein structural transition preceding the high-temperature transition (denaturation) was surprisingly found to coincide with a marked change in enzymatic activity for both LDHs...
June 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28624482/nmr-quantification-of-trimethylamine-n-oxide-in-human-serum-and-plasma-in-the-clinical-laboratory-setting
#6
Erwin Garcia, Justyna Wolak-Dinsmore, Zeneng Wang, Xinmin S Li, Dennis W Bennett, Margery A Connelly, James D Otvos, Stanley L Hazen, Elias J Jeyarajah
BACKGROUND AND OBJECTIVES: Trimethylamine-N-oxide (TMAO) produced by gut microbiota metabolism of dietary choline and carnitine has been shown to be associated with increased risk of cardiovascular disease (CVD) and to provide incremental clinical prognostic utility beyond traditional risk factors for assessing a patient's CVD risk. The aim of this study was to develop an automated nuclear magnetic resonance (NMR) spectroscopy assay for quantification of TMAO concentration in serum and plasma using a high-throughput NMR clinical analyzer...
June 14, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28621609/preoperative-serum-tmao-level-is-a-new-prognostic-marker-for-colorectal-cancer
#7
Xiaomei Liu, Heng Liu, Caijun Yuan, Yinxu Zhang, Wei Wang, Shuding Hu, Lei Liu, Ying Wang
AIM: This study is aimed to determine whether trimethylamine-N-oxide (TMAO) is a predictor of prognosis of patients with colorectal cancer. METHODS: Pretreatment TMAO serum levels were determined in 108 patients with colorectal cancer and 30 healthy controls. RESULTS: Median serum TMAO level was significantly higher in colorectal cancer patients than in healthy controls (p < 0.01). No correlation was observed between the disease-free survival and the type of chemotherapy regimen used, tumor location or lymphovascular invasion...
May 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/28611682/elevated-circulating-trimethylamine-n-oxide-levels-contribute-to-endothelial-dysfunction-in-aged-rats-through-vascular-inflammation-and-oxidative-stress
#8
Tiejun Li, Yanli Chen, Chaojun Gua, Xiaodong Li
Vascular endothelial dysfunction, a characteristic of the aging process, is an important risk factor for cardiovascular disease in aging. Although, vascular inflammation and oxidative stress are major contributors to endothelial dysfunction in aging, the underlying mechanisms during the aging process are not fully understood. Accumulating evidence reveals that gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) is implicated in the pathogenesis of many cardiovascular diseases. We tested the hypothesis that aging increases circulating TMAO levels, which induce vascular inflammation and oxidative stress, resulting in age-associated endothelial dysfunction...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28588885/elevated-trimethylamine-n-oxide-tmao-is-associated-with-poor-prognosis-in-primary-sclerosing-cholangitis-patients-with-normal-liver-function
#9
Martin Kummen, Mette Vesterhus, Marius Trøseid, Bjørn Moum, Asbjørn Svardal, Kirsten Muri Boberg, Pål Aukrust, Tom Hemming Karlsen, Rolf Kristian Berge, Johannes Roksund Hov
BACKGROUND: Trimethylamine-N-oxide (TMAO) is produced in the liver from trimethylamine, which is exclusively generated by gut bacteria. OBJECTIVE: The objective of this article is to investigate the relationship between TMAO and primary sclerosing cholangitis (PSC) and its clinical characteristics. METHODS: Serum TMAO was measured in 305 PSC patients, 90 ulcerative colitis patients and 99 healthy controls. RESULTS: In PSC patients with normal liver function (n = 197), TMAO was higher in patients reaching liver transplantation or death during follow-up than those who did not, with an optimal TMAO cut-off of 4...
June 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28588431/microbial-trimethylamine-n-oxide-as-a-disease-marker-something-fishy
#10
REVIEW
Bjarne Landfald, Jørgen Valeur, Arnold Berstad, Jan Raa
Production of trimethylamine-N-oxide (TMAO) via the gut microbiota has recently been proposed as an important pathophysiological mechanism linking ingestion of 'unhealthy foods', such as beef (containing carnitine) and eggs (containing choline), and the development of atherosclerosis. Hence, TMAO has gained attention as a novel biomarker for cardiovascular disease. However, fish and seafood contain considerable amounts of TMAO and are generally accepted as cardioprotective: a puzzling paradox that seems to have been neglected...
2017: Microbial Ecology in Health and Disease
https://www.readbyqxmd.com/read/28551440/osmolyte-induced-enhancement-of-expression-and-solubility-of-human-dihydrofolate-reductase-an-in-vivo-study
#11
Naira Rashid, Charu Thapliyal, Pratima Chaudhuri Chattopadhyay
The process of recombinant protein production in E. coli system is often hampered by the formation of insoluble aggregates. Human Dihydrofolate reductase (hDHFR), an enzyme involved in the synthesis of purine, thymidilate and several other amino acids like glycine, methionine and serine is highly aggregation prone. It catalyzes the reduction of dihydrofolate (H2F) in order to regenerate tetrahydrofolate (H4F) utilizing NADPH as a cofactor. We have attempted to ameliorate the production of soluble and functional protein by growing and inducing the cells under osmotic stress condition, in the presence of various osmolytes like glycerol, sorbitol, TMAO, proline and glycine at 37°C...
May 25, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28520899/increased-urinary-trimethylamine-n-oxide-tmao-following-cryptosporidium-infection-and-protein-malnutrition-independent-of-microbiome-effects
#12
D T Bolick, J Mayneris-Perxachs, G L Medlock, G L Kolling, J Papin, J R Swann, R L Guerrant
Cryptosporidium infections have been associated with growth stunting even in the absence of diarrhea. Having previously detailed the effects of protein deficiency on both microbiome and metabolome in this model, we now describe the specific gut microbial and biochemical effects of Cryptosporidium infection. Protein deficient mice were infected with Cryptosporidium parvum oocysts for 6-13 days and compared to uninfected controls. Following infection there was an increase in the urinary excretion of choline- and amino acid-derived metabolites...
May 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28515319/the-h-region-of-twin-arginine-signal-peptides-supports-productive-binding-of-bacterial-tat-precursor-proteins-to-the-tatbc-receptor-complex
#13
Agnes Ulfig, Julia Fröbel, Frank Lausberg, Anne-Sophie Blümmel, Anna Katharina Heide, Matthias Müller, Roland Freudl
The twin arginine translocation (Tat) pathway transports folded proteins across bacterial membranes. Tat precursor proteins possess a conserved twin-arginine (RR) motif in their signal peptides that is involved in their binding to the Tat translocase, but some facets of this interaction remain unclear. Here, we investigated the role of the hydrophobic (h-) region of the Escherichia coli TMAO reductase (TorA) signal peptide in TatBC receptor binding in vivo and in vitro. We show that besides the RR motif, a minimal functional h-region in the signal peptide is required for Tat-dependent export in E...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28511293/enterobacter-aerogenes-zdy01-attenuates-choline-induced-trimethylamine-n-oxide-levels-via-remodeling-gut-microbiota-in-mice
#14
Liang Qiu, Dong Yang, Xueying Tao, Jun Yu, Hua Xiong, Hua Wei
Trimethylamine N-oxide (TMAO), which is transformed from trimethylamine (TMA) through hepatic flavin-containing monooxygenases, can promote atherosclerosis. TMA is produced from dietary carnitine, phosphatidylcholine, and choline via the gut microbes. Previous works have shown that some small molecules, such as allicin, resveratrol, and 3,3-dimethyl-1-butanol, are used to reduce circulating TMAO levels. However, the use of bacteria as an effective therapy to reduce TMAO levels has not been reported. In the present study, 82 isolates were screened from healthy Chinese fecal samples on a basal salt medium supplemented with TMA as sole carbon source...
May 17, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28498348/nutrients-turned-into-toxins-microbiota-modulation-of-nutrient-properties-in-chronic-kidney-disease
#15
REVIEW
Raul Fernandez-Prado, Raquel Esteras, Maria Vanessa Perez-Gomez, Carolina Gracia-Iguacel, Emilio Gonzalez-Parra, Ana B Sanz, Alberto Ortiz, Maria Dolores Sanchez-Niño
In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects...
May 12, 2017: Nutrients
https://www.readbyqxmd.com/read/28479364/involvement-of-organic-cation-transporters-in-the-kinetics-of-trimethylamine-n-oxide
#16
Takeshi Miyake, Tadahaya Mizuno, Tatsuki Mochizuki, Miyuki Kimura, Shunji Matsuki, Shin Irie, Ichiro Ieiri, Maeda Kazuya, Hiroyuki Kusuhara
Recent studies suggest that trimethylamine N-oxide (TMAO) is associated with the development of chronic kidney disease and heart failure. In this study, we investigated the importance of organic cation transporters (OCTs) in the clearance and tissue distribution of TMAO. The low affinity and high capacity transport of TMAO by mouse and human OCT1 and OCT2 was observed. Uptake and efflux of TMAO by the mouse hepatocytes as well as TMAO uptake into mouse kidney slices were significantly decreased by the addition of tetraethylammonium or Oct1/2 double knockout (dKO)...
May 4, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28469156/impaired-renal-function-and-dysbiosis-of-gut-microbiota-contribute-to-increased-trimethylamine-n-oxide-in-chronic-kidney-disease-patients
#17
Kai-Yu Xu, Geng-Hong Xia, Jun-Qi Lu, Mu-Xuan Chen, Xin Zhen, Shan Wang, Chao You, Jing Nie, Hong-Wei Zhou, Jia Yin
Chronic kidney disease (CKD) patients have an increased risk of cardiovascular diseases (CVDs). The present study aimed to investigate the gut microbiota and blood trimethylamine-N-oxide concentration (TMAO) in Chinese CKD patients and explore the underlying explanations through the animal experiment. The median plasma TMAO level was 30.33 μmol/L in the CKD patients, which was significantly higher than the 2.08 μmol/L concentration measured in the healthy controls. Next-generation sequence revealed obvious dysbiosis of the gut microbiome in CKD patients, with reduced bacterial diversity and biased community constitutions...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28447688/influence-of-cosolvents-self-crowding-temperature-and-pressure-on-the-sub-nanosecond-dynamics-and-folding-stability-of-lysozyme
#18
S R Al-Ayoubi, P H Schummel, M Golub, J Peters, R Winter
We studied the effects of temperature and hydrostatic pressure on the dynamical properties and folding stability of highly concentrated lysozyme solutions in the absence and presence of the osmolytes trimethylamine-N-oxide (TMAO) and urea. Elastic incoherent neutron scattering (EINS) was applied to determine the mean-squared displacement (MSD) of the protein's hydrogen atoms to yield insights into the effects of these cosolvents on the averaged sub-nanosecond dynamics in the pressure range from ambient up to 4000 bar...
June 7, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28447460/effects-of-histidine-supplementation-on-global-serum-and-urine-1-h-nmr-based-metabolomics-and-serum-amino-acid-profiles-in-obese-women-from-a-randomized-controlled-study
#19
Shanshan Du, Shuhong Sun, Liyan Liu, Qiao Zhang, Fuchuan Guo, Chunlong Li, Rennan Feng, Changhao Sun
The aim of current study was to investigate the metabolic changes associated with histidine supplementation in serum and urine metabolic signatures and serum amino acid (AA) profiles. Serum and urine (1)H NMR-based metabolomics and serum AA profiles were employed in 32 and 37 obese women with metabolic syndrome (MetS) intervened with placebo or histidine for 12 weeks. Multivariable statistical analysis were conducted to define characteristic metabolites. In serum (1)H NMR metabolic profiles, increases in histidine, glutamine, aspartate, glycine, choline, and trimethylamine-N-oxide (TMAO) were observed; meanwhile, decreases in cholesterol, triglycerides, fatty acids and unsaturated lipids, acetone, and α/β-glucose were exhibited after histidine supplement...
June 2, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28439531/genome-and-cd4-t-cell-methylome-wide-association-study-of-circulating-trimethylamine-n-oxide-in-the-genetics-of-lipid-lowering-drugs-and-diet-network-goldn
#20
Stella Aslibekyan, Marguerite R Irvin, Bertha A Hidalgo, Rodney T Perry, Elias J Jeyarajah, Erwin Garcia, Irina Shalaurova, Paul N Hopkins, Michael A Province, Hemant K Tiwari, Jose M Ordovas, Devin M Absher, Donna K Arnett
BACKGROUND: Trimethylamine-N-oxide (TMAO), an atherogenic metabolite species, has emerged as a possible new risk factor for cardiovascular disease. Animal studies have shown that circulating TMAO levels are regulated by genetic and environmental factors. However, large-scale human studies have failed to replicate the observed genetic associations, and epigenetic factors such as DNA methylation have never been examined in relation to TMAO levels. METHODS AND RESULTS: We used data from the family-based Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to investigate the heritable determinants of plasma TMAO in humans...
June 2017: Journal of Nutrition & Intermediary Metabolism
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