-
1دورية أكاديمية
المؤلفون: Wang, Jingxuan, Bakker, Wouter, Zheng, Weijia, de Haan, Laura, Rietjens, Ivonne M.C.M., Bouwmeester, Hans
المصدر: Archives of Toxicology 96 (2022) 5 ; ISSN: 0340-5761
مصطلحات موضوعية: Bile acid reabsorption, Bile acid transporters, Conjugated bile acids, Deoxynivalenol
الوصف: Conjugated bile acids are synthesized in liver and subsequently secreted into the intestinal lumen from which they are actively reabsorbed and transported back to liver. The efficient enterohepatic circulation of conjugated bile acids is important to maintain homeostasis. The mycotoxin deoxynivalenol (DON) is a fungal secondary metabolite that contaminates cereal food. Upon human exposure, it can cause intestinal dysfunction. We explored the effects of DON exposure on the intestinal absorption of conjugated bile acids and the expression of bile acid transporters using an in vitro model based on Caco-2 cell layers grown in transwells. Our study shows that the transport rate of taurocholic acid (TCA) is decreased after 48-h pre-exposure of the Caco-2 cells to 2 µM DON, which is a realistic intestinal DON concentration. Exposure to DON downregulates expression of the genes coding for the apical sodium-dependent bile acid transporter (ASBT), the ileal bile acid-binding protein (IBABP) and the organic solute transporter α (OSTα), and it counteracts the agonist activity of Farnesoid X receptor (FXR) agonist GW4064 on these genes. In addition, the transport of ten taurine or glycine-conjugated bile acids in a physiological relevant mixture by the intestinal Caco-2 cell layers was decreased after pre-exposure of the cells to DON, pointing at a potential for DON-mediated accumulation of the conjugated bile acids at the intestinal luminal side. Together the results reveal that DON inhibits intestinal bile acid reabsorption by reducing the expression of bile acid transporters thereby affecting bile acid intestinal kinetics, leading to bile acid malabsorption in the intestine. Our study provides new insights into the hazards of DON exposure.
وصف الملف: application/pdf
العلاقة: https://edepot.wur.nl/566575Test; https://research.wur.nl/en/publications/exposure-to-the-mycotoxin-deoxynivalenol-reduces-the-transport-ofTest
الإتاحة: https://doi.org/10.1007/s00204-022-03256-8Test
https://research.wur.nl/en/publications/exposure-to-the-mycotoxin-deoxynivalenol-reduces-the-transport-ofTest -
2
المؤلفون: Jingxuan Wang, Wouter Bakker, Weijia Zheng, Laura de Haan, Ivonne M. C. M. Rietjens, Hans Bouwmeester
المصدر: Archives of Toxicology, 96(5), 1473-1482
Archives of Toxicology 96 (2022) 5مصطلحات موضوعية: Bile acid transporters, Health, Toxicology and Mutagenesis, General Medicine, Mycotoxins, Toxicology, digestive system, Deoxynivalenol, Bile Acids and Salts, Intestines, Humans, Caco-2 Cells, Trichothecenes, Conjugated bile acids, Bile acid reabsorption, Toxicologie, VLAG
الوصف: Conjugated bile acids are synthesized in liver and subsequently secreted into the intestinal lumen from which they are actively reabsorbed and transported back to liver. The efficient enterohepatic circulation of conjugated bile acids is important to maintain homeostasis. The mycotoxin deoxynivalenol (DON) is a fungal secondary metabolite that contaminates cereal food. Upon human exposure, it can cause intestinal dysfunction. We explored the effects of DON exposure on the intestinal absorption of conjugated bile acids and the expression of bile acid transporters using an in vitro model based on Caco-2 cell layers grown in transwells. Our study shows that the transport rate of taurocholic acid (TCA) is decreased after 48-h pre-exposure of the Caco-2 cells to 2 µM DON, which is a realistic intestinal DON concentration. Exposure to DON downregulates expression of the genes coding for the apical sodium-dependent bile acid transporter (ASBT), the ileal bile acid-binding protein (IBABP) and the organic solute transporter α (OSTα), and it counteracts the agonist activity of Farnesoid X receptor (FXR) agonist GW4064 on these genes. In addition, the transport of ten taurine or glycine-conjugated bile acids in a physiological relevant mixture by the intestinal Caco-2 cell layers was decreased after pre-exposure of the cells to DON, pointing at a potential for DON-mediated accumulation of the conjugated bile acids at the intestinal luminal side. Together the results reveal that DON inhibits intestinal bile acid reabsorption by reducing the expression of bile acid transporters thereby affecting bile acid intestinal kinetics, leading to bile acid malabsorption in the intestine. Our study provides new insights into the hazards of DON exposure.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4e32d66e427e75a4c8d172a33b5ab2e9Test
https://doi.org/10.1007/s00204-022-03256-8Test -
3دورية أكاديمية
المؤلفون: Dawn E. Telford, Jane Y. Edwards, Sara M. Lipson, Brian Sutherland, P.Hugh R. Barrett, John R. Burnett, Elaine S. Krul, Bradley T. Keller, Murray W. Huff
المصدر: Journal of Lipid Research, Vol 44, Iss 5, Pp 943-952 (2003)
مصطلحات موضوعية: bile acid reabsorption, atorvastatin, kinetics, cholesterol 7α-hydroxylase, LDL receptor, Biochemistry, QD415-436
الوصف: Discovery of the ileal apical sodium-dependent bile acid transporter (ASBT) permitted development of specific inhibitors of bile acid reabsorption, potentially a new class of cholesterol-lowering agents. In the present study, we tested the hypothesis that combining the novel ASBT inhibitor, SC-435, with the HMG-CoA reductase inhibitor, atorvastatin, would potentiate reductions in LDL cholesterol (LDL-C) and LDL apolipoprotein B (apoB). ApoB kinetic studies were performed in miniature pigs fed a typical human diet and treated with the combination of SC-435 (5 mg/kg/day) plus atorvastatin (3 mg/kg/day) (SC-435+A) or a placebo. SC-435+A decreased plasma total cholesterol by 23% and LDL-C by 40%. Multicompartmental analysis (SAAM II) demonstrated that LDL apoB significantly decreased by 35% due primarily to a 45% increase in the LDL apoB fractional catabolic rate (FCR). SC-435+A significantly decreased hepatic concentrations of free cholesterol and cholesteryl ester, and increased hepatic LDL receptor mRNA consequent to increased cholesterol 7α-hydroxylase expression and activity. In comparison, SC-435 (10 mg/kg/day) monotherapy decreased LDL apoB by 10% due entirely to an 18% increase in LDL apoB FCR, whereas atorvastatin monotherapy (3 mg/kg/day) decreased LDL apoB by 30% due primarily to a 22% reduction in LDL apoB production.We conclude that SC-435+A potentiates the reduction of LDL-C and LDL apoB due to complementary mechanisms of action.
وصف الملف: electronic resource
العلاقة: http://www.sciencedirect.com/science/article/pii/S0022227520311408Test; https://doaj.org/toc/0022-2275Test
-
4دورية أكاديمية
المؤلفون: Out, Carolien, Patankar, Jay V., Doktorova, Marcela, Boesjes, Marije, Bos, Trijnie, de Boer, Sanna, Havinga, Rick, Wolters, Henk, Boverhof, Renze, van Dijk, Theo H., Smoczek, Anna, Bleich, Andre, Sachdev, Vinay, Kratky, Dagmar, Kuipers, Folkert, Verkade, Henkjan J., Groen, Albert K.
المصدر: Out , C , Patankar , J V , Doktorova , M , Boesjes , M , Bos , T , de Boer , S , Havinga , R , Wolters , H , Boverhof , R , van Dijk , T H , Smoczek , A , Bleich , A , Sachdev , V , Kratky , D , Kuipers , F , Verkade , H J & Groen , A K 2015 , ' Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4 ' , Journal of Hepatology , vol. 63 , no. 3 , pp. ....
مصطلحات موضوعية: Gut microbiota, Intestinal bacteria, Antibiotic treatment, Enterohepatic circulation, Germfree, Fgf15, Asbt, Gata4, Bile acid reabsorption, Bile acid synthesis, Cyp7a1, LIVER MICROSOMAL METABOLISM, MOUSE SMALL-INTESTINE, GERMFREE RATS, CONVENTIONAL RATS, CHOLESTEROL, STEROIDS, MICE, ABSORPTION, EXPRESSION
الوصف: Background & Aims: Regulation of bile acid homeostasis in mammals is a complex process regulated via extensive cross-talk between liver, intestine and intestinal microbiota. Here we studied the effects of gut microbiota on bile acid homeostasis in mice. Methods: Bile acid homeostasis was assessed in four mouse models. Germfree mice, conventionally-raised mice, Asbt-KO mice and intestinal-specific Gata4-iKO mice were treated with antibiotics (bacitracin, neomycin and vancomycin; 100 mg/kg) for five days and subsequently compared with untreated mice. Results: Attenuation of the bacterial flora by antibiotics strongly reduced fecal excretion and synthesis of bile acids, but increased the expression of the bile acid synthesis enzyme CYP7A1. Similar effects were seen in germfree mice. Intestinal bile acid absorption was increased and accompanied by increases in plasma bile acid levels, biliary bile acid secretion and enterohepatic cycling of bile acids. In the absence of microbiota, the expression of the intestinal bile salt transporter Asbt was strongly increased in the ileum and was also expressed in more proximal parts of the small intestine. Most of the effects of antibiotic treatment on bile acid homeostasis could be prevented by genetic inactivation of either Asbt or the transcription factor Gata4. Conclusions: Attenuation of gut microbiota alters Gata4-controlled expression of Asbt, increasing absorption and decreasing synthesis of bile acids. Our data support the concept that under physiological conditions microbiota stimulate Gata4, which suppresses Asbt expression, limiting the expression of this transporter to the terminal ileum. Our studies expand current knowledge on the bacterial control of bile acid homeostasis. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
الإتاحة: https://doi.org/10.1016/j.jhep.2015.04.030Test
https://hdl.handle.net/11370/0e1a1fb2-eac2-4871-b808-50239aef400cTest
https://research.rug.nl/en/publications/0e1a1fb2-eac2-4871-b808-50239aef400cTest -
5
المؤلفون: P. Hugh R. Barrett, Sara M. Lipson, Elaine S. Krul, Jane Y. Edwards, Bradley T. Keller, John R. Burnett, Murray W. Huff, Dawn E. Telford, Brian G. Sutherland
المصدر: Journal of Lipid Research, Vol 44, Iss 5, Pp 943-952 (2003)
مصطلحات موضوعية: Male, Time Factors, Apolipoprotein B, Atorvastatin, Reductase, Biochemistry, chemistry.chemical_compound, Endocrinology, biology, Bile acid, Symporters, Reabsorption, bile acid reabsorption, atorvastatin, Lipoproteins, LDL, HMG-CoA reductase, Cholesteryl ester, Swine, Miniature, Female, lipids (amino acids, peptides, and proteins), medicine.drug, medicine.medical_specialty, medicine.drug_class, Lipoproteins, Organic Anion Transporters, Sodium-Dependent, QD415-436, digestive system, Cyclic N-Oxides, Internal medicine, medicine, Animals, Pyrroles, RNA, Messenger, Apolipoproteins B, Dose-Response Relationship, Drug, cholesterol 7α-hydroxylase, nutritional and metabolic diseases, LDL receptor, Cell Biology, Cholesterol, LDL, chemistry, Receptors, LDL, Heptanoic Acids, kinetics, biology.protein, Hydroxymethylglutaryl CoA Reductases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Carrier Proteins, Tropanes
الوصف: Discovery of the ileal apical sodium-dependent bile acid transporter (ASBT) permitted development of specific inhibitors of bile acid reabsorption, potentially a new class of cholesterol-lowering agents. In the present study, we tested the hypothesis that combining the novel ASBT inhibitor, SC-435, with the HMG-CoA reductase inhibitor, atorvastatin, would potentiate reductions in LDL cholesterol (LDL-C) and LDL apolipoprotein B (apoB). ApoB kinetic studies were performed in miniature pigs fed a typical human diet and treated with the combination of SC-435 (5 mg/kg/day) plus atorvastatin (3 mg/kg/day) (SC-435+A) or a placebo. SC-435+A decreased plasma total cholesterol by 23% and LDL-C by 40%. Multicompartmental analysis (SAAM II) demonstrated that LDL apoB significantly decreased by 35% due primarily to a 45% increase in the LDL apoB fractional catabolic rate (FCR). SC-435+A significantly decreased hepatic concentrations of free cholesterol and cholesteryl ester, and increased hepatic LDL receptor mRNA consequent to increased cholesterol 7alpha-hydroxylase expression and activity. In comparison, SC-435 (10 mg/kg/day) monotherapy decreased LDL apoB by 10% due entirely to an 18% increase in LDL apoB FCR, whereas atorvastatin monotherapy (3 mg/kg/day) decreased LDL apoB by 30% due primarily to a 22% reduction in LDL apoB production. We conclude that SC-435+A potentiates the reduction of LDL-C and LDL apoB due to complementary mechanisms of action.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f99ab019940c1ee77f91fab67fd27c6Test
http://www.sciencedirect.com/science/article/pii/S0022227520311408Test -
6دورية أكاديمية
المؤلفون: Jinxin Liu (311455), Yu Wang (12152), Lamei Xue (6717716), Chenzhipeng Nie (7861862), Juan Sun (439334), Mingcong Fan (6717719), Haifeng Qian (179918), Li Wang (15202), Yan Li (23143)
مصطلحات موضوعية: Biochemistry, Genetics, Molecular Biology, Physiology, Ecology, Science Policy, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Novel Metabolic Regulation, scavenger receptor class B type, bile acid homeostasis, HMGCR, bile acid excretion, bile acid metabolism, bile acid reabsorption, whole-grain diets, 3- hydroxy -3-methylglutaryl reductase, Whole-Grain-Diet-Fed Mice Hyperchol., ABCG, feed conversion ratio, ATP, LDLR, polypeptide 1, SR-BI, CYP, bile acid synthesis, TG, TC
الوصف: Hypercholesterolemia is a major risk factor for chronic metabolic diseases. Nevertheless, a whole-grain diet could ameliorate this issue in a number of ways, including by regulating bile acid metabolism. However, the potential mechanism is unclear. The aim of the current study is to explore the effects of whole-grain diets (brown rice diet and whole wheat diet) on bile acid homeostasis. After intervention for 8 weeks in mouse model, whole-grain diets showed reduced feed conversion ratio, and the lipid levels (total cholesterol (TC) and triglycerides (TG)) were also meliorated in the serum and liver of mice. Moreover, whole-grain diets reduced the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) (cholesterol synthesis) in the liver of mice. Interestingly, whole-grain diets not only promoted the mRNA expressions of low-density lipoprotein receptor (LDLR), ATP binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SR-BI) (reverse cholesterol transport) but also facilitated the expressions of cytochrome P450, family 7, subfamily a, polypeptide 1 (CYP7a1) and cytochrome P450, family 27, subfamily a, polypeptide 1 (CYP27a1) (bile acid synthesis). Further study found that whole-grain diets promoted intestinal bile acid reabsorption and reduced bile acid excretion. Our study provided a novel metabolic regulation of bile acids in response to reduced cholesterol levels induced by whole-grain diets.
النص الكامل