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Bile acid metabolism

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https://www.readbyqxmd.com/read/28209601/the-influence-of-rosuvastatin-upon-the-gastrointestinal-microbiota-and-host-gene-expression-profiles
#1
James A Nolan, Peter Henry Skuse, Kalaimathi Govindarajan, Elaine Patterson, Nina Konstantinidou, Patrick G Casey, John MacSharry, Fergus Shanahan, Catherine Stanton, Colin Hill, P D Cotter, Susan A Joyce, Cormac Gm Gahan
Statins are the most widely prescribed medications worldwide for the treatment of hypercholesterolemia. They inhibit the activity of 3-hydroxy-3-methylglutaryl co enzyme A reductase (HMG-R) an enzyme involved in cholesterol synthesis in higher organisms and in isoprenoid biosynthesis in some bacteria. We hypothesized that statins may influence the microbial community in the gut through either direct inhibition or indirect mechanisms involving alterations to host responses. We therefore examined the impact of rosuvastatin (RSV) on the community structure of the murine gastrointestinal microbiota...
February 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28203044/a-case-of-sitosterolemia-due-to-compound-heterozygous-mutations-in-abcg5-clinical-features-and-treatment-outcomes-obtained-with-colestimide-and-ezetimibe
#2
Sahoko Ono, Junko Matsuda, Aki Saito, Takenobu Yamamoto, Wataru Fujimoto, Hitomi Shimizu, Sumito Dateki, Kazunobu Ouchi
Sitosterolemia is a rare, autosomal recessively inherited disorder of lipid metabolism caused by mutations in the "ATP-binding cassette, subfamily G" member 5 and 8 proteins (encoded by the ABCG5 and ABCG8 genes, respectively), which play critical roles in the intestinal and biliary excretion of plant sterols. We report the clinical features and treatment outcomes of an 18-month-old Japanese girl with sitosterolemia, who presented with multiple linear and intertriginous xanthomas around the joint areas. Serum lipid analyses revealed elevated levels of total cholesterol (T-Chol: 866 mg/dL), low density lipoprotein-cholesterol (LDL-C: 679 mg/dL), and plant sterols (sitosterol: 24...
January 2017: Clinical Pediatric Endocrinology: Case Reports and Clinical Investigations: Official Journal of the Japanese Society for Pediatric Endocrinology
https://www.readbyqxmd.com/read/28199845/host-genotype-and-gut-microbiome-modulate-insulin-secretion-and-diet-induced-metabolic-phenotypes
#3
Julia H Kreznar, Mark P Keller, Lindsay L Traeger, Mary E Rabaglia, Kathryn L Schueler, Donald S Stapleton, Wen Zhao, Eugenio I Vivas, Brian S Yandell, Aimee Teo Broman, Bruno Hagenbuch, Alan D Attie, Federico E Rey
Genetic variation drives phenotypic diversity and influences the predisposition to metabolic disease. Here, we characterize the metabolic phenotypes of eight genetically distinct inbred mouse strains in response to a high-fat/high-sucrose diet. We found significant variation in diabetes-related phenotypes and gut microbiota composition among the different mouse strains in response to the dietary challenge and identified taxa associated with these traits. Follow-up microbiota transplant experiments showed that altering the composition of the gut microbiota modifies strain-specific susceptibility to diet-induced metabolic disease...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28192465/impact-of-a-cafeteria-diet-and-daily-physical-training-on-the-rat-serum-metabolome
#4
Susana Suárez-García, Josep M Del Bas, Antoni Caimari, Rosa M Escorihuela, Lluís Arola, Manuel Suárez
Regular physical activity and healthy dietary patterns are commonly recommended for the prevention and treatment of metabolic syndrome (MetS), which is diagnosed at an alarmingly increasing rate, especially among adolescents. Nevertheless, little is known regarding the relevance of physical exercise on the modulation of the metabolome in healthy people and those with MetS. We have previously shown that treadmill exercise ameliorated different symptoms of MetS. The aim of this study was to investigate the impact of a MetS-inducing diet and different intensities of aerobic training on the overall serum metabolome of adolescent rats...
2017: PloS One
https://www.readbyqxmd.com/read/28191525/obesity-diabetes-and-the-role-of-bile-acids-in-metabolism
#5
Gerald H Tomkin, Daphne Owens
Bile acids have many activities over and above their primary function in aiding absorption of fat and fat soluble vitamins. Bile acids are synthesized from cholesterol, and thus are involved in cholesterol homeostasis. Bile acids stimulate glucagon-like peptide 1 (GLP1) production in the distal small bowel and colon, stimulating insulin secretion, and therefore, are involved in carbohydrate and fat metabolism. Bile acids through their insulin sensitising effect play a part in insulin resistance and type 2 diabetes...
June 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28188341/evaluation-of-transcriptomic-signature-as-a-valuable-tool-to-study-drug-induced-cholestasis-in-primary-human-hepatocytes
#6
Céline Parmentier, Philippe Couttet, Armin Wolf, Thomas Zaccharias, Bruno Heyd, Philippe Bachellier, Marianne Uteng, Lysiane Richert
Primary human hepatocyte (PHH) sandwich cultures from five different donors were daily exposed to cyclosporine A (CsA), ibuprofen (IBU), chlorpromazine (CPZ), amiodarone (AMI) and paracetamol (APAP) at their respective Cmax (total) for short-term (1-3 days) and long-term treatment (14 days). Whole genome mRNA profiles (34,693 genes in total) were conducted using an Illumina microarray platform. The impact of compound treatments on gene signatures involved in liver differentiation, cholestasis and in bile acid homeostasis was evaluated...
February 10, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28186768/the-impact-of-gut-microbiota-mediated-bile-acid-metabolism-on-the-solubilization-capacity-of-bile-salt-micelles-and-drug-solubility
#7
Elaine F Enright, Susan A Joyce, Cormac G M Gahan, Brendan T Griffin
In recent years, the gut microbiome has gained increasing appreciation as a determinant of the health status of the human host. Bile salts that are secreted into the intestine may be biotransformed by enzymes produced by the gut bacteria. To date, bile acid research at the host-microbe interface has primarily been directed toward effects on host metabolism. The aim of this work was to investigate the effect of changes in gut microbial bile acid metabolism on the solubilization capacity of bile salt micelles and consequently intraluminal drug solubility...
February 10, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28178326/quantitative-liver-proteomics-identifies-fgf19-targets-that-couple-metabolism-and-proliferation
#8
Vittoria Massafra, Alexandra Milona, Harmjan R Vos, Boudewijn M T Burgering, Saskia W C van Mil
Fibroblast growth factor 19 (FGF19) is a gut-derived peptide hormone that is produced following activation of Farnesoid X Receptor (FXR). FGF19 is secreted and signals to the liver, where it contributes to the homeostasis of bile acid (BA), lipid and carbohydrate metabolism. FGF19 is a promising therapeutic target for the metabolic syndrome and cholestatic diseases, but enthusiasm for its use has been tempered by FGF19-mediated induction of proliferation and hepatocellular carcinoma. To inform future rational design of FGF19-variants, we have conducted temporal quantitative proteomic and gene expression analyses to identify FGF19-targets related to metabolism and proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28176778/reconciled-rat-and-human-metabolic-networks-for-comparative-toxicogenomics-and-biomarker-predictions
#9
Edik M Blais, Kristopher D Rawls, Bonnie V Dougherty, Zhuo I Li, Glynis L Kolling, Ping Ye, Anders Wallqvist, Jason A Papin
The laboratory rat has been used as a surrogate to study human biology for more than a century. Here we present the first genome-scale network reconstruction of Rattus norvegicus metabolism, iRno, and a significantly improved reconstruction of human metabolism, iHsa. These curated models comprehensively capture metabolic features known to distinguish rats from humans including vitamin C and bile acid synthesis pathways. After reconciling network differences between iRno and iHsa, we integrate toxicogenomics data from rat and human hepatocytes, to generate biomarker predictions in response to 76 drugs...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28174747/a-disease-associated-microbial-and-metabolomics-state-in-relatives-of-pediatric-inflammatory-bowel-disease-patients
#10
Jonathan P Jacobs, Maryam Goudarzi, Namita Singh, Maomeng Tong, Ian H McHardy, Paul Ruegger, Miro Asadourian, Bo-Hyun Moon, Allyson Ayson, James Borneman, Dermot P B McGovern, Albert J Fornace, Jonathan Braun, Marla Dubinsky
BACKGROUND & AIMS: Microbes may increase susceptibility to inflammatory bowel disease (IBD) by producing bioactive metabolites that affect immune activity and epithelial function. We undertook a family based study to identify microbial and metabolic features of IBD that may represent a predisease risk state when found in healthy first-degree relatives. METHODS: Twenty-one families with pediatric IBD were recruited, comprising 26 Crohn's disease patients in clinical remission, 10 ulcerative colitis patients in clinical remission, and 54 healthy siblings/parents...
November 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28167213/metagenomics-approach-to-the-study-of-the-gut-microbiome-structure-and-function-in-zebrafish-danio-rerio-fed-with-gluten-formulated-diet
#11
Hyunmin Koo, Joseph A Hakim, Mickie L Powell, Ranjit Kumar, Peter G Eipers, Casey D Morrow, Michael Crowley, Elliot J Lefkowitz, Stephen A Watts, Asim K Bej
In this study, we report the gut microbial composition and predictive functional profiles of zebrafish, Danio rerio, fed with a control formulated diet (CFD), and a gluten formulated diet (GFD) using metagenomics approach and bioinformatics tools. The microbial communities of the GFD-fed D. rerio displayed heightened abundances of Legionellales, Rhizobiaceae, and Rhodobacter, as compared to the CFD-fed counterparts. Predicted metagenomics of microbial communities (PICRUSt) in GFD-fed D. rerio showed KEGG functional categories corresponding to bile secretion, secondary bile acid biosynthesis, and the metabolism of glycine, serine, and threonine...
February 3, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28166818/resistant-starch-can-improve-insulin-sensitivity-independently-of-the-gut-microbiota
#12
Laure B Bindels, Rafael R Segura Munoz, João Carlos Gomes-Neto, Valentin Mutemberezi, Inés Martínez, Nuria Salazar, Elizabeth A Cody, Maria I Quintero-Villegas, Hatem Kittana, Clara G de Los Reyes-Gavilán, Robert J Schmaltz, Giulio G Muccioli, Jens Walter, Amanda E Ramer-Tait
BACKGROUND: Obesity-related diseases, including type 2 diabetes and cardiovascular disease, have reached epidemic proportions in industrialized nations, and dietary interventions for their prevention are therefore important. Resistant starches (RS) improve insulin sensitivity in clinical trials, but the mechanisms underlying this health benefit remain poorly understood. Because RS fermentation by the gut microbiota results in the formation of physiologically active metabolites, we chose to specifically determine the role of the gut microbiota in mediating the metabolic benefits of RS...
February 7, 2017: Microbiome
https://www.readbyqxmd.com/read/28157235/possible-involvement-of-nitric-oxide-in-enhanced-liver-injury-and-fibrogenesis-during-cholestasis-in-cytoglobin-deficient-mice
#13
Tuong Thi Van Thuy, Le Thi Thanh Thuy, Katsutoshi Yoshizato, Norifumi Kawada
This study clarified the role of Cygb, the fourth globin in mammals originally discovered in rat hepatic stellate cells (HSCs), in cholestatic liver disease. Bile duct ligation (BDL) augmented inflammatory reactions as revealed by increased infiltrating neutrophils, CD68(+)-macrophages, and chemokine expression in Cygb(-/-) mice. In these mice, impairment of bile canalicular indicated by the loss of CD10 expression, down-regulation of bile salt transporters, increased total bile acid, and massive apoptotic and necrotic hepatocytes occurred with the release of cytochrome c, activation of caspase 3, resulting in reduced animal survival compared to wild-type mice...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28153841/cholic-acid-feeding-leads-to-increased-cyp2d6-expression-in-cyp2d6-humanized-mice
#14
Xian Pan, Rebecca Kent, Kyoung-Jae Won, Hyunyoung Jeong
Cytochrome P450 2D6 (CYP2D6) is a major drug-metabolizing enzyme, but factors governing transcriptional regulation of its expression remain poorly understood. Based on previous reports of small heterodimer partner (SHP) playing an important role as a transcriptional repressor of CYP2D6 expression, here we investigated how a known upstream regulator of SHP expression, namely cholestasis triggered by cholic acid (CA) feeding in mice, can lead to altered CYP2D6 expression. To this end, CYP2D6-humanized (Tg-CYP2D6) mice were fed with CA-supplemented or control diet for 14 days, and hepatic expression of multiple genes was examined...
February 2, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28153708/steroidogenic-acute-regulatory-protein-star-overexpression-attenuates-hfd-induced-hepatic-steatosis-and-insulin-resistance
#15
Yanyan Qiu, Xianxian Sui, Yongkun Zhan, Chen Xu, Xiaobo Li, Yanxia Ning, Xiuling Zhi, Lianhua Yin
Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology. Intracellular lipid accumulation is the first step in the development and progression of NAFLD. Steroidogenic acute regulatory protein (StAR) plays an important role in the synthesis of bile acid and intracellular lipid homeostasis and cholesterol metabolism. We hypothesize that StAR is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. The hypothesis was identified using free fatty acid (FFA)-overloaded NAFLD in vitro model and high-fat diet (HFD)-induced NAFLD mouse model transfected by recombinant adenovirus encoding StAR (StAR)...
January 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28145001/treatment-with-the-natural-fxr-agonist-chenodeoxycholic-acid-reduces-clearance-of-plasma-ldl-whilst-decreasing-circulating-pcsk9-lipoprotein-a-and-apolipoprotein-c-iii
#16
M Ghosh Laskar, M Eriksson, M Rudling, B Angelin
BACKGROUND: The natural farnesoid X receptor (FXR) agonist chenodeoxycholic acid (CDCA) suppresses hepatic cholesterol and bile acid synthesis and reduces biliary cholesterol secretion and triglyceride production. Animal studies have shown that bile acids downregulate hepatic LDL receptors (LDLRs); however, information on LDL metabolism in humans is limited. METHODS: Kinetics of autologous (125) I-LDL were determined in 12 male subjects at baseline and during treatment with CDCA (15 mg kg(-1) day(-1) )...
February 1, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28139067/the-effects-of-graded-levels-of-calorie-restriction-ix-global-metabolomic-screen-reveals-modulation-of-carnitines-sphingolipids-and-bile-acids-in-the-liver-of-c57bl-6-mice
#17
Cara L Green, Sharon E Mitchell, Davina Derous, Yingchun Wang, Luonan Chen, Jing-Dong J Han, Daniel E L Promislow, David Lusseau, Alex Douglas, John R Speakman
Calorie restriction (CR) remains the most robust intervention to extend lifespan and improve health span. Using a global mass spectrometry-based metabolomic approach, we identified 193 metabolites that were significantly differentially expressed (SDE) in the livers of C57BL/6 mice, fed graded levels of CR (10, 20, 30 and 40% CR) compared to mice fed ad libitum for 12 h a day. The differential expression of metabolites also varied with the different feeding groups. Pathway analysis revealed that graded CR had an impact on carnitine synthesis and the carnitine shuttle pathway, sphingosine-1-phosphate (S1P) signalling and methionine metabolism...
January 31, 2017: Aging Cell
https://www.readbyqxmd.com/read/28130274/commensal-bacteria-at-the-crossroad-between-cholesterol-homeostasis-and-chronic-inflammation-in-atherosclerosis
#18
Kazuyuki Kasahara, Takeshi Tanoue, Tomoya Yamashita, Keiko Yodoi, Takuya Matsumoto, Takuo Emoto, Taiji Mizoguchi, Tomohiro Hayashi, Naoki Kitano, Naoto Sasaki, Koji Atarashi, Kenya Honda, Ken-Ichi Hirata
The gut microbiota were shown to play critical roles in the development of atherosclerosis, but the detailed mechanism is limited. The purpose of this study is to clarify the influence of gut microbiota on atherogenesis via lipid metabolism and systemic inflammation. Germ-free (GF) or conventionally raised (Conv) Apolipoprotein E deficient (ApoE(-/-)) mice were fed chow diet and sacrificed at twenty weeks of age. We found lack of gut microbiota in ApoE(-/-) mice caused a significant increase in the plasma and hepatic cholesterol levels compared to ConvR ApoE(-/-) mice...
January 27, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28130067/farnesoid-x-receptor-activation-promotes-hepatic-amino-acid-catabolism-and-ammonium-clearance-in-mice
#19
Vittoria Massafra, Alexandra Milona, Harmjan R Vos, Rúben J J Ramos, Johan Gerrits, Ellen C L Willemsen, José M Ramos Pittol, Noortje Ijssennagger, Martin Houweling, Hubertus C M T Prinsen, Nanda M Verhoeven-Duif, Boudewijn M Burgering, Saskia W C van Mil
BACKGROUND & AIMS: The nuclear receptor subfamily 1 group H member 4 (NR1H4 or farnesoid X receptor, FXR) regulates bile acid synthesis, transport, and catabolism. FXR also regulates post-prandial lipid and glucose metabolism. We performed quantitative proteomic analyses of liver tissues from mice to evaluate these functions and investigate whether FXR regulates amino acid metabolism. METHODS: To study the role of FXR in mouse liver, we used mice with a disruption of Nr1h4 (FXR-knockout mice) and compared them to floxed control mice...
January 24, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28128437/schisandrol-b-protects-against-cholestatic-liver-injury-through-pregnane-x-receptor
#20
Hang Zeng, Yiming Jiang, Pan Chen, Xiaomei Fan, Dongshun Li, Aiming Liu, Xiaochao Ma, Wen Xie, Peiqing Liu, Frank J Gonzalez, Min Huang, Huichang Bi
BACKGROUND AND PURPOSE: Currently, ursodeoxycholic acid is the only FDA-approved drug for limited cholestatic liver diseases, and thus the development of new therapeutic approaches is of great importance. This study aimed to evaluate the anti-cholestasis effect of Schisandrol B (SolB), a bioactive compound isolated from Schisandra sphenanthera. EXPERIMENTAL APPROACH: Hepatoprotective effect of SolB against lithocholic acid (LCA)-induced intrahepatic extrahepatic cholestasis was evaluated in mice...
January 27, 2017: British Journal of Pharmacology
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