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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
#1
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
https://www.readbyqxmd.com/read/28434257/ratio-of-serum-levels-of-ages-to-soluble-rage-is-correlated-with-trimethylamine-n-oxide-in-non-diabetic-subjects
#2
Atsuko Tahara, Nobuhiro Tahara, Sho-Ichi Yamagishi, Akihiro Honda, Sachiyo Igata, Yoshikazu Nitta, Munehisa Bekki, Tomohisa Nakamura, Yoichi Sugiyama, Jiahui Sun, Masayoshi Takeuchi, Makiko Shimizu, Hiroshi Yamazaki, Kei Fukami, Yoshihiro Fukumoto
Trimethylamine (TMA), an intestinal microflora-dependent metabolite formed from phosphatidylcholine- and L-carnitine-rich food, such as red meat, is further converted to trimethylamine-N-oxide (TMAO), which could play a role in cardiometabolic disease. Red meat-derived products are one of the major environmental sources of advanced glycation end products (AGEs) that may also contribute to the pathogenesis of cardiometabolic disorders through the interaction with receptor for AGEs (RAGE). However, the relationship among AGEs, soluble form of RAGE (sRAGE) and TMAO in humans remains unclear...
April 23, 2017: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/28433924/the-metabolic-fate-of-isotopically-labeled-trimethylamine-n-oxide-tmao-in-humans
#3
Siraphat Taesuwan, Clara E Cho, Olga V Malysheva, Erica Bender, Julia H King, Jian Yan, Anna E Thalacker-Mercer, Marie A Caudill
Trimethylamine-N-oxide (TMAO) is associated with chronic disease risk. However, little is known about the metabolic fate of dietary TMAO. This study sought to quantitatively elucidate the metabolic fate of orally consumed TMAO in humans. As part of a crossover feeding study, healthy young men (n=40) consumed 50-mg deuterium-labeled methyl d9-TMAO (d9-TMAO), and enrichments of TMAO and its derivatives were measured in blood for 6 h, urine and stool, as well as skeletal muscle in a subset of men (n=6). Plasma d9-TMAO was detected as early as 15 min, increased until 1 h and remained elevated through the 6-h period...
April 13, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28432876/effect-of-pistachio-consumption-on-the-modulation-of-urinary-gut-microbiota-related-metabolites-in-prediabetic-subjects
#4
Pablo Hernández-Alonso, Daniel Cañueto, Simona Giardina, Jordi Salas-Salvadó, Nicolau Cañellas, Xavier Correig, Mònica Bulló
The specific nutritional composition of nuts could affect different metabolic pathways involved in a broad range of metabolic diseases. We therefore investigated whether chronic consumption of pistachio nuts modifies the urine metabolome in prediabetic subjects. We designed a randomized crossover clinical trial in 39 prediabetic subjects. They consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out...
April 12, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28407784/relationships-between-gut-microbiota-plasma-metabolites-and-metabolic-syndrome-traits-in-the-metsim-cohort
#5
Elin Org, Yuna Blum, Silva Kasela, Margarete Mehrabian, Johanna Kuusisto, Antti J Kangas, Pasi Soininen, Zeneng Wang, Mika Ala-Korpela, Stanley L Hazen, Markku Laakso, Aldons J Lusis
BACKGROUND: The gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gut microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study. RESULTS: We investigate gut microbiota relationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gut microbiota and fasting serum levels of a number of metabolites, including fatty acids, amino acids, lipids, and glucose...
April 13, 2017: Genome Biology
https://www.readbyqxmd.com/read/28389555/targeting-of-microbe-derived-metabolites-to-improve-human-health-the-next-frontier-for-drug-discovery
#6
J Mark Brown, Stanley L Hazen
Recent advances in metabolomic and genome mining approaches have uncovered a poorly understood metabolome that originates solely or in part from bacterial enzyme sources. Whether living on exposed surfaces or within our intestinal tract, our microbial inhabitants produce a remarkably diverse set of natural products and small molecule metabolites that can impact human health and disease. Highlighted here, the gut microbe-derived metabolite trimethylamine N-oxide (TMAO) has been causally linked to the development of cardiovascular diseases...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28378399/osmolyte-effects-on-the-conformational-dynamics-of-a-dna-hairpin-at-ambient-and-extreme-environmental-conditions
#7
Satyajit Patra, Christian Anders, Nelli Erwin, Roland Winter
The structural dynamics of a DNA hairpin (Hp) are studied in the absence and presence of the two natural osmolytes trimethylamine-N-oxide (TMAO) and urea at ambient and extreme environmental conditions, including high pressures and high temperatures, by using single-molecule Förster resonance energy transfer and fluorescence correlation spectroscopy. The effect of pressure on the conformational dynamics of the DNA Hp is investigated on a single-molecule level, providing novel mechanistic insights into its conformational conversions...
April 5, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28377725/gut-microbiota-dependent-metabolite-trimethylamine-n-oxide-contributes-to-cardiac-dysfunction-in-western-diet-induced-obese-mice
#8
Kui Chen, Xiaoqian Zheng, Mingchen Feng, Dongliang Li, Hongqi Zhang
Excessive consumption of diets high in sugars and saturated fat, frequently known as western diet (WD), may lead to obesity and metabolic syndrome. Recent evidence shows that WD-induced obesity impairs cardiac function, but the underlying mechanisms are not fully understood. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of specific dietary nutrients, has emerged as a key contributor to cardiovascular disease pathogenesis. We tested the hypothesis that elevated circulating TMAO levels contribute to cardiac dysfunction in WD-induced obesity...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28377341/-a-machine-learning-model-using-gut-microbiome-data-for-predicting-changes-of-trimethylamine-n-oxide-in-healthy-volunteers-after-choline-consumption
#9
Jun-Qi Lu, Shan Wang, Jia Yin, Shan Wu, Yan He, Hui-Min Zheng, Hua-Fang Sheng, Hong-Wei Zhou
OBJECTIVE: To establish a machine learning model based on gut microbiota for predicting the level of trimethylamine N-oxide (TMAO) metabolism in vivo after choline intake to provide guidance of individualized precision diet and evidence for screening population at high risks of cardiovascular disease. METHODS: We quantified plasma levels of TMAO in 18 healthy volunteers before and 8 h after a choline challenge (ingestion of two boiled eggs). The volunteers were divided into two groups with increased or decreased TMAO level following choline challenge...
March 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28356058/hiv-infected-persons-with-type-2-diabetes-show-evidence-of-endothelial-dysfunction-and-increased-inflammation
#10
Malene Hove-Skovsgaard, Julie Christine Gaardbo, Lilian Kolte, Kamilla Winding, Ingebjørg Seljeflot, Asbjørn Svardal, Rolf Kristian Berge, Jan Gerstoft, Henrik Ullum, Marius Trøseid, Susanne Dam Nielsen
BACKGROUND: Increased incidence of cardiovascular diseases (CVD) in both HIV infection and type 2 diabetes (T2D) compared to the general population has been described. Little is known about the combined effect of HIV infection and T2D on inflammation and endothelial function, both of which may contribute to elevated risk of CVD. METHODS: Cross-sectional study including 50 HIV-infected persons on combination anti-retroviral therapy (cART), with HIV RNA <200 copies/mL (n = 25 with T2D (HIV + T2D+), n = 25 without T2D (HIV + T2D-)) and 50 uninfected persons (n = 22 with T2D (HIV-T2D+) and n = 28 without T2D (HIV-T2D-))...
March 29, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28301576/restored-mutant-receptor-corticoid-binding-in-chaperone-complexes-by-trimethylamine-n-oxide
#11
Aaron L Miller, W Austin Elam, Betty H Johnson, Shagufta H Khan, Raj Kumar, E Brad Thompson
Without a glucocorticoid (GC) ligand, the transcription factor glucocorticoid receptor (GR) is largely cytoplasmic, with its GC-binding domain held in high affinity conformation by a cluster of chaperones. Binding a GC causes serial dis- and re-associations with chaperones, translocation of the GR to the nucleus, where it binds to DNA sites and associates with coregulatory proteins and basic transcription complexes. Herein, we describe the effects of a potent protective osmolyte, trimethylamine N-oxide (TMAO), on a conditions-dependent "activation-labile" mutant GR (GRact/l), which under GR-activating conditions cannot bind GCs in cells or in cell cytosols...
2017: PloS One
https://www.readbyqxmd.com/read/28293920/the-intriguing-link-between-the-intestinal-microbiota-and-cardiovascular-disease
#12
Giuseppe Lippi, Elisa Danese, Camilla Mattiuzzi, Emmanuel J Favaloro
Human microbiota is a term conventionally used to define the normal flora of microbes living in all of us, most of which are resident in the gastrointestinal tract. Despite it having been known for some time that the vast majority of intestinal bacteria exert a strong influence on human life, recent technologic breakthroughs have made it possible to more accurately characterize the host microbial communities and explore their relationship with many human diseases. Notably, the evidence accumulated over the past 10 years suggests that a reasonable relationship can now be established between gut microbiota composition and the risk of cardiovascular disease...
March 14, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28265960/impact-of-bariatric-surgery-on-metabolic-and-gut-microbiota-profile-a-systematic-review-and-meta-analysis
#13
REVIEW
Dimitrios E Magouliotis, Vasiliki S Tasiopoulou, Eleni Sioka, Christina Chatedaki, Dimitrios Zacharoulis
We aim to review the available literature on obese patients treated with bariatric procedures, in order to assess their effect on the metabolic and gut microbiota profiles. A systematic literature search was performed in PubMed, Cochrane library, and Scopus databases, in accordance with the PRISMA guidelines. Twenty-two studies (562 patients) met the inclusion criteria. This study points to significant amelioration of postoperative levels of glucose, insulin, triglycerides, total cholesterol, LDL, HDL, HOMA-IR, food intake, and diabetes remission...
March 6, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28228526/trimethylamine-n-oxide-stabilizes-proteins-via-a-distinct-mechanism-compared-with-betaine-and-glycine
#14
Yi-Ting Liao, Anthony C Manson, Michael R DeLyser, William G Noid, Paul S Cremer
We report experimental and computational studies investigating the effects of three osmolytes, trimethylamine N-oxide (TMAO), betaine, and glycine, on the hydrophobic collapse of an elastin-like polypeptide (ELP). All three osmolytes stabilize collapsed conformations of the ELP and reduce the lower critical solution temperature (LSCT) linearly with osmolyte concentration. As expected from conventional preferential solvation arguments, betaine and glycine both increase the surface tension at the air-water interface...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28218056/regulation-of-the-escherichia-coli-ydhy-t-operon-in-the-presence-of-alternative-electron-acceptors
#15
Naji Al Ibrahim, Jeffrey Green
The Escherichia coli K-12 ydhY-T operon, coding for a predicted oxidoreductase complex, is activated under anaerobic conditions and repressed in the presence of nitrate or nitrite. Anaerobic activation is mediated by the transcription factor FNR and nitrate/nitrite repression is mediated by NarXL and NarQP. In vitro transcription reactions revealed that the DNA upstream of ydhY-T contains sufficient information for RNA polymerase alone to initiate transcription from five locations. FNR severely inhibited synthesis of two of these transcripts (located upstream of, and within, the FNR binding site) and activated the FNR-dependent promoter previously identified in vivo...
February 3, 2017: Microbiology
https://www.readbyqxmd.com/read/28196478/genetic-analysis-of-impaired-trimethylamine-metabolism-using-whole-exome-sequencing
#16
Yiran Guo, Liang-Dar Hwang, Jiankang Li, Jason Eades, Chung Wen Yu, Corrine Mansfield, Alexis Burdick-Will, Xiao Chang, Yulan Chen, Fujiko F Duke, Jianguo Zhang, Steven Fakharzadeh, Paul Fennessey, Brendan J Keating, Hui Jiang, Hakon Hakonarson, Danielle R Reed, George Preti
BACKGROUND: Trimethylaminuria (TMAU) is a genetic disorder whereby people cannot convert trimethylamine (TMA) to its oxidized form (TMAO), a process that requires the liver enzyme FMO3. Loss-of-function variants in the FMO3 gene are a known cause of TMAU. In addition to the inability to metabolize TMA precursors like choline, patients often emit a characteristic odor because while TMAO is odorless, TMA has a fishy smell. The Monell Chemical Senses Center is a research institute with a program to evaluate people with odor complaints for TMAU...
February 15, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28191513/dietary-cholesterol-and-egg-yolk-should-be-avoided-by-patients-at-risk-of-vascular-disease
#17
REVIEW
J David Spence
Recent recommendations that limits to dietary cholesterol be dropped were probably heavily influenced by propaganda from the egg industry. After conviction for false advertising, the industry has spent hundreds of millions of dollars to convince the public, physicians, and policy makers that dietary cholesterol and egg yolk are harmless. However, there are good reasons for longstanding recommendations that dietary cholesterol be limited to <200 mg/ day in persons at risk of vascular disease. It is seldom understood that this essentially means all people in developed countries who expect to attain an advanced age...
April 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28176881/functional-coupling-of-human-microphysiology-systems-intestine-liver-kidney-proximal-tubule-blood-brain-barrier-and-skeletal-muscle
#18
Lawrence Vernetti, Albert Gough, Nicholas Baetz, Sarah Blutt, James R Broughman, Jacquelyn A Brown, Jennifer Foulke-Abel, Nesrin Hasan, Julie In, Edward Kelly, Olga Kovbasnjuk, Jonathan Repper, Nina Senutovitch, Janet Stabb, Catherine Yeung, Nick C Zachos, Mark Donowitz, Mary Estes, Jonathan Himmelfarb, George Truskey, John P Wikswo, D Lansing Taylor
Organ interactions resulting from drug, metabolite or xenobiotic transport between organs are key components of human metabolism that impact therapeutic action and toxic side effects. Preclinical animal testing often fails to predict adverse outcomes arising from sequential, multi-organ metabolism of drugs and xenobiotics. Human microphysiological systems (MPS) can model these interactions and are predicted to dramatically improve the efficiency of the drug development process. In this study, five human MPS models were evaluated for functional coupling, defined as the determination of organ interactions via an in vivo-like sequential, organ-to-organ transfer of media...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28169544/correction-to-comparison-of-different-tmao-force-fields-and-their-impact-on-the-folding-equilibrium-of-a-hydrophobic-polymer
#19
Francisco Rodríguez-Ropero, Philipp Rötzscher, Nico F A van der Vegt
No abstract text is available yet for this article.
February 7, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28153917/trimethylamine-n-oxide-in-atherogenesis-impairing-endothelial-self-repair-capacity-and-enhancing-monocyte-adhesion
#20
GuoHua Ma, Bing Pan, Yue Chen, CaiXia Guo, MingMing Zhao, LeMin Zheng, BuXing Chen
Several studies have reported a strong association between high plasma level of trimethylamine N-oxide (TMAO) and atherosclerosis development. However, the exact mechanism underlying this correlation is unknown. In the present study, we try to explore the impact of TMAO on endothelial dysfunction. After TMAO treatment, human umbilical vein endothelial cells (HUVECs) showed significant impairment in cellular proliferation and HUVECs-extracellular matrix (ECM) adhesion compared with control. Likewise, TMAO markedly suppressed HUVECs migration in transwell migration assay and wound healing assay...
April 30, 2017: Bioscience Reports
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