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Bile acid metabolism

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https://www.readbyqxmd.com/read/28453831/sortilin-1-loss-of-function-protects-against-cholestatic-liver-injury-by-attenuating-hepatic-bile-acid-accumulation-in-bile-duct-ligated-mice
#1
Jibiao Li, Benjamin L Woolbright, Wen Zhao, Yifeng Wang, David Matye, Bruno Hagenbuch, Hartmut Jaeschke, Tiangang Li
Sortilin 1 (Sort1) is an intracellular trafficking receptor that mediates protein sorting in the endocytic or secretory pathways. Recent studies revealed a role of Sort1 in the regulation of cholesterol and bile acid metabolism. This study further investigated the role of Sort1 in modulating bile acid detoxification and cholestatic liver injury in bile duct ligated mice. We found that Sort1 KO mice had attenuated liver injury 24 h after BDL, which was mainly attributed to less bile infarct formation. Sham-operated Sort1 KO mice had about 20% larger bile acid pool size than sham-operated WT mice, but 24 h after BDL Sort1 KO mice had significantly attenuated hepatic bile acid accumulation and smaller bile acid pool size...
April 26, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28453659/udp-glucuronosyltransferase-ugt-2b-subfamily-interspecies-differences-in-carnivores
#2
Takamitsu Kondo, Yoshinori Ikenaka, Shouta M M Nakayama, Yusuke K Kawai, Hazuki Mizukawa, Yoko Mitani, Kei Nomyama, Shinsuke Tanabe, Mayumi Ishizuka
UDP-glucuronosyltransferases (UGTs) are among the most important xenobiotic metabolizing enzymes that conjugate a wide range of chemicals. Previous studies showed that Felidae and Pinnipedia species have very low UGT activities toward some phenolic compounds because of the UGT1A6 pseudogene and small numbers of UGT1A isozymes. In addition to the UGT1As, UGT2Bs isozymes also conjugate various endogenous (e.g., estrogens, androgens, and bile acids) and exogenous compounds (opioids, NSAIDs, and environmental pollutants)...
April 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28448890/metabolic-profiles-of-neotuberostemonine-and-tuberostemonine-in-rats-by-high-performance-liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry
#3
Yongbin Tong, Weitong Xu, Yan Wu, Liting Ou, Mian Zhang, Xianghong Xu, Chaofeng Zhang
Neotuberostemonine (NS) and tuberostemonine (TS), a pair of stereoisomers, are the active components contained in Stemona tuberosa, an antitussive herbal medicine in China. Two isomers have different pharmacological efficacies, which will be related with their in vivo disposition. However, the metabolic fates of NS and TS remain unknown. A method of high performance liquid chromatography/quadrupole time-of-flight mass spectrometry coupled with mass detect filter technique was established to investigate the metabolites in rat plasma, bile, urine, and feces after oral administration of the equal doses of NS and TS...
April 17, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28446193/liver-morphometrics-and-metabolic-blood-profile-across-divergent-phenotypes-for-feed-efficiency-in-the-bovine
#4
Yuri Regis Montanholi, Livia Sadocco Haas, Kendall Carl Swanson, Brenda Lee Coomber, Shigeto Yamashiro, Stephen Paul Miller
BACKGROUND: Feed costs are a major expense in the production of beef cattle. Individual variation in the efficiency of feed utilization may be evident through feed efficiency-related phenotypes such as those related to major energetic sinks. Our objectives were to assess the relationships between feed efficiency with liver morphometry and metabolic blood profile in feedlot beef cattle. METHODS: Two populations (A = 112 and B = 45) of steers were tested for feed efficiency...
April 26, 2017: Acta Veterinaria Scandinavica
https://www.readbyqxmd.com/read/28446062/metabolite-sensing-g-protein-coupled-receptors-facilitators-of-diet-related-immune-regulation
#5
Jian K Tan, Craig McKenzie, Eliana Mariño, Laurence Macia, Charles R Mackay
Nutrition and the gut microbiome regulate many systems, including the immune, metabolic, and nervous systems. We propose that the host responds to deficiency (or sufficiency) of dietary and bacterial metabolites in a dynamic way, to optimize responses and survival. A family of G protein-coupled receptors (GPCRs) termed the metabolite-sensing GPCRs bind to various metabolites and transmit signals that are important for proper immune and metabolic functions. Members of this family include GPR43, GPR41, GPR109A, GPR120, GPR40, GPR84, GPR35, and GPR91...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28442498/identification-and-characterization-of-a-novel-ppar%C3%AE-regulated-and-7%C3%AE-hydroxyl-bile-acid-preferring-cytosolic-sulfotransferase-ml-stl-sult2a8
#6
Lu Feng, Yee-Lok Yuen, Jian Xu, Xing Liu, Martin Yan-Chun Chan, Kai Wang, Wing-Ping Fong, Wing-Tai Cheung, Susanna Sau-Tuen Lee
PPARα has been known to play a pivotal role in orchestrating lipid, glucose, and amino acid metabolism via transcriptional regulation of its target genes expression during energy deprivation. Recent evidence also suggesting PPARα is involved in bile acid metabolism, but how PPARα modulates the homeostasis of bile acids during fasting is still not clear. In a mechanistic study aiming to dissect the spectrum of PPARα target genes involved in metabolic response to fasting, we identified a novel mouse gene (herein named mL-STL) which shared extensive homology to Sult2a subfamily of a superfamily of cytosolic sulfotransferases, implying its potential function in sulfonation...
April 25, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28434196/role-of-gut-microbiota-bile-acids-and-their-crosstalk-in-the-effects-of-bariatric-surgery-on-obesity-and-type-2-diabetes
#7
Haijun Liu, Cheng Hu, Xueli Zhang, Weiping Jia
Type 2 diabetes mellitus is becoming increasingly prevalent worldwide and has become one of the greatest threats to global health. Bariatric surgery was initially designed to achieve weight loss and subsequently was noted to induce improvements or remission of type 2 diabetes. Currently, these bariatric operations such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the most effective procedures for the treatment of obesity and type 2 diabetes mellitus worldwide. However, the specific mechanism mediating the beneficial effects of metabolic surgery has remained largely unknown...
April 23, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28429701/-microbiota-and-metabolic-syndrome
#8
Yüksel Altuntaş, Adnan Batman
The role of gut bacteria in the pathogenesis and treatment of various diseases has been a focus of attention in the last 10 years. Prevalence of diabetes, obesity, and cardiovascular diseases continues to increase, in spite of technological developments and treatment alternatives. Microbial dysbiosis, described as the decrease of useful bacteria and the increase of harmful bacteria, has been associated with diabetes, obesity, atherosclerosis, and metabolic syndrome. In microbial dysbiosis, increase of harmful metabolites and changes to composition of bile acids occur via carbohydrate and protein fermentation...
April 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28428001/cholesterol-and-related-sterols-autoxidation
#9
REVIEW
Chiara Zerbinati, Luigi Iuliano
Cholesterol is a unique lipid molecule providing the building block for membranes, hormone, vitamin D and bile acid synthesis. Metabolism of cholesterol involves several enzymes acting on the sterol nucleus or the iso-octyl tail. In the recent years, research interest has been focused on oxysterols, cholesterol derivatives generated by the addition of oxygen to the cholesterol backbone. Oxysterols can be produced enzymatically or by autoxidation. Autoxidation of cholesterol proceeds through type I or type II mechanisms...
April 17, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28425490/urinary-and-fecal-metabonomics-study-of-the-protective-effect-of-chaihu-shu-gan-san-on-antibiotic-induced-gut-microbiota-dysbiosis-in-rats
#10
Meng Yu, Hong-Mei Jia, Chao Zhou, Yong Yang, Li-Li Sun, Zhong-Mei Zou
Accumulating evidence suggests that the gut microbiota dysbiosis and their host metabolic phenotype alteration is an important factor in human disease development. A traditional Chinese herbal formula, Chaihu-Shu-Gan-San (CSGS), has been effectively used in the treatment of various gastrointestinal (GI) disorders. The present study was carried out to investigate whether CSGS modulates the host metabolic phenotype under the condition of gut microbiota dysbiosis. The metabonomics studies of biochemical changes in urine and feces of antibiotic-induced gut microbiota dysbiosis rats after treatment with CSGS were performed using UPLC-Q-TOF/MS...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424617/targeting-bile-acid-receptors-discovery-of-a-potent-and-selective-farnesoid-x-receptor-agonist-as-a-new-lead-in-the-pharmacological-approach-to-liver-diseases
#11
Carmen Festa, Simona De Marino, Adriana Carino, Valentina Sepe, Silvia Marchianò, Sabrina Cipriani, Francesco S Di Leva, Vittorio Limongelli, Maria C Monti, Angela Capolupo, Eleonora Distrutti, Stefano Fiorucci, Angela Zampella
Bile acid (BA) receptors represent well-defined targets for the development of novel therapeutic approaches to metabolic and inflammatory diseases. In the present study, we report the generation of novel C-3 modified 6-ethylcholane derivatives. The pharmacological characterization and molecular docking studies for the structure-activity rationalization, allowed the identification of 3β-azido-6α-ethyl-7α-hydroxy-5β-cholan-24-oic acid (compound 2), a potent and selective FXR agonist with a nanomolar potency in transactivation assay and high efficacy in the recruitment of SRC-1 co-activator peptide in Alfa Screen assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424615/huangqin-decoction-attenuates-cpt-11-induced-gastrointestinal-toxicity-by-regulating-bile-acids-metabolism-homeostasis
#12
Xu Wang, Dong-Ni Cui, Xiao-Min Dai, Jing Wang, Wei Zhang, Zun-Jian Zhang, Feng-Guo Xu
Irinotecan (CPT-11) is a potent chemotherapeutic agent, however, its clinical usage is often limited by the induction of severe gastrointestinal (GI) toxicity, especially late-onset diarrhea. HuangQin Decoction (HQD), commonly used for the treatment of GI ailments, has been proved could significantly ameliorate the intestinal toxicity of CPT-11. To reveal the mechanisms of CPT-11-induced toxicity and the modulation effects of HQD, a previous untargeted metabolomics study was performed and the results indicated that HQD may protect the GI tract by altering the metabolism of bile acids (BAs)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28422755/%C3%AE-klotho-deficiency-protects-against-obesity-through-a-crosstalk-between-liver-microbiota-and-brown-adipose-tissue
#13
Emmanuel Somm, Hugues Henry, Stephen J Bruce, Sébastien Aeby, Marta Rosikiewicz, Gerasimos P Sykiotis, Mohammed Asrih, François R Jornayvaz, Pierre Damien Denechaud, Urs Albrecht, Moosa Mohammadi, Andrew Dwyer, James S Acierno, Kristina Schoonjans, Lluis Fajas, Gilbert Greub, Nelly Pitteloud
β-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and FGF15/19 signaling. Klb-/- mice are refractory to beneficial action of pharmacological FGF21 treatment including stimulation of glucose utilization and thermogenesis. Here, we investigated the energy homeostasis in Klb-/- mice on high-fat diet in order to better understand the consequences of abrogating both endogenous FGF15/19 and FGF21 signaling during caloric overload. Surprisingly, Klb-/- mice are resistant to diet-induced obesity (DIO) owing to enhanced energy expenditure and BAT activity...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28420126/novel-genetic-variants-associated-with-child-refractory-esophageal-stricture-with-food-allergy-by-exome-sequencing
#14
Min Yang, Min Xiong, Huan Chen, Lanlan Geng, Peiyu Chen, Jing Xie, Shui Qing Ye, Ding-You Li, Sitang Gong
BACKGROUND: Refractory esophageal stricture (RES) may be attributed to food allergy. Its etiology and pathogenesis are not fully understood. Identification of novel genetic variants associated with this disease by exome sequencing (exome-seq) may provide new mechanistic insights and new therapeutic targets. METHODS: To identify new and novel disease-associating variants, whole-exome sequencing was performed on an Illumina NGS platform in three children with RES as well as food allergy...
April 15, 2017: Nutrients
https://www.readbyqxmd.com/read/28418859/serum-metabolomics-differentiating-pancreatic-cancer-from-new-onset-diabetes
#15
Xiangyi He, Jie Zhong, Shuwei Wang, Yufen Zhou, Lei Wang, Yongping Zhang, Yaozong Yuan
To establish a screening strategy for pancreatic cancer (PC) based on new-onset diabetic mellitus (NO-DM), serum metabolomics analysis and a search for the metabolic pathways associated with PC related DM were performed. Serum samples from patients with NO-DM (n = 30) and patients with pancreatic cancer and NO-DM were examined by liquid chromatography-mass spectrometry. Data were analyzed using principal components analysis (PCA) and orthogonal projection to latent structures (OPLS) of the most significant metabolites...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416481/western-diet-deregulates-bile-acid-homeostasis-cell-proliferation-and-tumorigenesis-in-colon
#16
Denis Dermadi, Satu Valo, Saara Ollila, Rabah Soliymani, Nina Sipari, Marjaana Pussila, Laura Sarantaus, Jere Linden, Marc Baumann, Minna Nyström
Western-style diets (WD) high in fat and scarce in fiber and vitamin D increase risks of colorectal cancer (CRC). Here we performed a long-term diet study in mice to follow tumorigenesis and characterize structural and metabolic changes in colon mucosa associated with WD and predisposition to CRC. WD increased colon tumor numbers and mucosa proteomic analysis indicated severe deregulation of intracellular bile acid (BA) homeostasis and activation of cell proliferation. WD also increased crypt depth and colon cell proliferation...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28414465/topical-intestinal-aminoimidazole-agonists-of-g-protein-coupled-bile-acid-receptor-1-promote-glucagon-like-peptide-1-secretion-and-improve-glucose-tolerance
#17
Manuel Lasalle, Vanessa Hoguet, Nathalie Hennuyer, Florence Leroux, Catherine Piveteau, Loic Belloy, Sophie Lestavel, Emmanuelle Vallez, Emilie Dorchies, Isabelle Duplan, Emmanuel Sevin, Maxime Culot, Fabien Gosselet, Rajaa Boulahjar, Adrien Herledan, Bart Staels, Benoit Deprez, Anne Tailleux, Julie Charton
The role of the G-Protein-coupled Bile Acid Receptor TGR5 in various organs, tissues and cell types, specifically in intestinal endocrine L-cells and brown adipose tissue, has made it a promising therapeutical target in several diseases, especially type-2 diabetes and metabolic syndrome. However, recent studies have shown deleterious on-target effects of systemic TGR5 agonists. To avoid these systemic effects while stimulating Glucagon Like Peptide-1 (GLP-1) secreting enteroendocrine L-cells, we have designed TGR5 agonists with low intestinal permeability...
April 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28413172/the-effects-of-metformin-on-fibroblast-growth-factor-19-21-and-fibroblast-growth-factor-receptor-1-in-high-fat-diet-and-streptozotocin-induced-diabetic-rats
#18
Yan Wang, Ningning Dang, Pei Sun, Jin Xia, Chunxue Zhang, Shuguang Pang
To understand metformin’s effects on fibroblast growth factors (FGFs) and fibroblast growth factor receptor 1 (FGFR1), we investigated circulating fibroblast growth factor-19 (FGF19), FGF21 levels, and FGFR1 in type 2 diabetes mellitus (T2DM). In addition, protein kinase B (Akt) signaling pathway was detected to explain the possible mechanisms. T2DM was induced by feeding rats with high-fat diet for 11 weeks, followed by a low dose of streptozotocin (STZ, 30-35 mg/kg, intraperitoneally). Control rats (Con) were fed on a normal chow; diabetic rats (DM) were fed on high-fat diet supplemented with or without metformin (METF) for 12 weeks (500 mg・kg(-1)・d(-1))...
April 11, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28411380/metabolic-profile-of-obeticholic-acid-and-endogenous-bile-acids-in-rats-with-decompensated-liver-cirrhosis
#19
Aldo Roda, Rita Aldini, Cecilia Camborata, Silvia Spinozzi, Placido Franco, Massimiliano Cont, Antonia D'Errico, Francesco Vasuri, Alessio Degiovanni, Lorenzo Maroni, Luciano Adorini
Obeticholic acid (OCA) is a semisynthetic bile acid (BA) analogue and potent farnesoid X receptor agonist approved to treat cholestasis. We evaluated the biodistribution and metabolism of OCA administered to CCl4 -induced cirrhotic rats. This was to ascertain if plasma and hepatic concentrations of OCA are potentially more harmful than those of endogenous BA. After administration of OCA (30 mg/kg), we used liquid chromatography-mass spectrometry to measure OCA, its metabolites, and BA at different time-points in various organs and fluids...
April 14, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28409465/peroxisomal-membrane-and-matrix-protein-import-using-a-semi-intact-mammalian-cell-system
#20
Kanji Okumoto, Masanori Honsho, Yuqiong Liu, Yukio Fujiki
Peroxisomes are essential intracellular organelles that catalyze a number of essential metabolic pathways including β-oxidation of very long chain fatty acids, synthesis of plasmalogen, bile acids, and generation and degradation of hydrogen peroxide. These peroxisomal functions are accomplished by strictly and spatiotemporally regulated compartmentalization of the enzymes catalyzing these reactions. Defects in peroxisomal protein import result in inherited peroxisome biogenesis disorders in humans. Peroxisomal matrix and membrane proteins are synthesized on free ribosomes and transported to peroxisomes in a manner dependent on their specific targeting signals and their receptors...
2017: Methods in Molecular Biology
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