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Lin Chen, Lu Liao, Ting Zhai, Xiangtao Huang, Yong Chen
BACKGROUND AND OBJECTIVE: Borneol, a traditional Chinese medicine (TCM), is often orally co-administered with other TCM and chemical drugs, but the drug-drug interactions between borneol and the other compounds remains unclear. This work investigates the effect of orally administered borneol on the transcription and expression of hepatic uptake transporters (Ntcp, Oatp2b1, Oatp1a1, Oatp1a4, Oct1, Oct2, Octn2 and Oat2) and efflux transporters (Mdrla, Mrp2, Mrp4 and Mrp5) in rats, aiming to obtain essential information to guide its clinical applications...
August 13, 2018: European Journal of Drug Metabolism and Pharmacokinetics
Gang Wang, Tao Han, ShiJia Wang, Min Chen, Yueming Sun, Zan Fu
To investigate the role of the peroxisome proliferator-activated receptor- γ (PPAR γ ) in the progression of cholesterol gallstone disease (CGD), C57bl/6J mice were randomized to the following groups (n=7/group): L (lithogenic diet, LGD), LM (LGD+pioglitazone), CM (chow diet+pioglitazone), and NC (normal control, chow diet). Gallbladder stones were observed by microscopy. Histological gallbladder changes were assessed. Bile acids (BA) and cholesterol were measured in the serum, bile, and feces. Proteins and mRNA expression of genes involved in BA metabolism and enterohepatic circulation were assessed by western blotting and real-time RT-PCR...
2018: BioMed Research International
Lino Arisqueta, Hiart Navarro-Imaz, Ibone Labiano, Yuri Rueda, Olatz Fresnedo
High fat diet (HFD) feeding or leptin deficient mice are extensively used as models resembling features of human non-alcoholic fatty liver disease (NAFLD). The concurrence of experimental factors as fat content and source or total caloric intake leads to prominent differences in the development of the hepatic steatosis and related disturbances. In this work, we characterized the hepatic lipid accumulation induced by HFD in wild type (Wt) and ob/ob mice with the purpose of differentiating adaptations to HFD from those specific of increased overfeeding due to leptin deficiency-associated hyperphagia...
August 10, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Peter Hegyi, Joszef Maléth, Julian R Walters, Alan F Hofmann, Stephen J Keely
Epithelial cells line the entire surface of the gastrointestinal tract and its accessory organs where they primarily function in transporting digestive enzymes, nutrients, electrolytes, and fluid to and from the luminal contents. At the same time, epithelial cells are responsible for forming a physical and biochemical barrier that prevents the entry into the body of harmful agents, such as bacteria and their toxins. Dysregulation of epithelial transport and barrier function is associated with the pathogenesis of a number of conditions throughout the intestine, such as inflammatory bowel disease, chronic diarrhea, pancreatitis, reflux esophagitis, and cancer...
October 1, 2018: Physiological Reviews
Shou-Yan Wu, Shi-Chao Cui, Le Wang, Yi-Ting Zhang, Xiao-Xia Yan, Heng-Lei Lu, Guo-Zhen Xing, Jin Ren, Li-Kun Gong
Cholestasis is a common feature of liver injury, which manifests as bile acid excretion and/or enterohepatic circulation disorders. However, very few effective therapies exist for cholestasis. Recently, 18β-Glycyrrhetinic acid (18b-GA), a major metabolic component of glycyrrhizin, which is the main ingredient of licorice, was reported to protect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. However, its protective mechanism remains unclear. We hypothesized that 18b-GA may stimulate the signaling pathway of bile acid (BA) transportation in hepatocytes, resulting its hepatoprotective effect...
July 30, 2018: Acta Pharmacologica Sinica
Kelly E Mercer, Sudeepa Bhattacharyya, Maria Elena Diaz-Rubio, Brian D Piccolo, Lindsay M Pack, Neha Sharma, Mousumi Chaudhury, Mario A Cleves, Sree V Chintapalli, Kartik Shankar, Martin J J Ronis, Laxmi Yeruva
Background: During the postnatal feeding period, formula-fed infants have higher cholesterol synthesis rates and lower circulating cholesterol concentrations than their breastfed counterparts. Although this disparity has been attributed to the uniformly low dietary cholesterol content of typical infant formulas, little is known of the underlying mechanisms associated with this altered cholesterol metabolism phenotype. Objective: We aimed to determine the molecular etiology of diet-associated changes in early-life cholesterol metabolism with the use of a postnatal piglet feeding model...
May 1, 2018: Journal of Nutrition
Marta Calatayud Arroyo, Tom Van de Wiele, Emma Hernandez-Sanabria
The interplay between host and microbiota has been long recognized and extensively described. The mouth is similar to other sections of the gastrointestinal tract, as resident microbiota occurs and prevents colonisation by exogenous bacteria. Indeed, more than 600 species of bacteria are found in the oral cavity, and a single individual may carry around 100 different at any time. Oral bacteria possess the ability to adhere to the various niches in the oral ecosystem, thus becoming integrated within the resident microbial communities, and favouring growth and survival...
July 4, 2018: Journal of Visualized Experiments: JoVE
Chang Yeob Han
Farnesoid X receptor (FXR), a metabolic nuclear receptor, plays critical roles in the maintenance of systemic energy homeostasis and the integrity of many organs, including liver and intestine. It regulates bile acid, lipid, and glucose metabolism, and contributes to inter-organ communication, in particular the enterohepatic signaling pathway, through bile acids and fibroblast growth factor-15/19 (FGF-15/19). The metabolic effects of FXR are also involved in gut microbiota. In addition, FXR has various functions in the kidney, adipose tissue, pancreas, cardiovascular system, and tumorigenesis...
July 16, 2018: International Journal of Molecular Sciences
John P Kennelly, Jelske N van der Veen, Randal C Nelson, Kelly-Ann Leonard, Rick Havinga, Jean Buteau, Folkert Kuipers, Rene L Jacobs
De novo phosphatidylcholine (PC) synthesis via CTP:phosphocholine cytidylyltransferase-α (CTα) is required for very-low-density lipoprotein secretion. To determine the precise role of de novo PC synthesis in intestinal lipid metabolism, we deleted CTα exclusively in the intestinal epithelium of mice (CTαIKO mice). When fed a chow diet, CTαIKO mice showed normal fat absorption despite a ~30% decrease in intestinal PC concentrations relative to control mice, suggesting that biliary PC can fully support chylomicron secretion under these conditions...
July 14, 2018: Journal of Lipid Research
Cecile Karrer, Thomas Roiss, Natalie von Goetz, Darja Gramec Skledar, Lucija Peterlin Mašič, Konrad Hungerbühler
BACKGROUND: The endocrine disrupting chemical bisphenol A (BPA) has been facing stricter regulations in recent years. BPA analogs, such as the bisphenols S, F, and AF (BPS, BPF, and BPAF) are increasingly used as replacement chemicals, although they were found to exert estrogenic effects similar to those of BPA. Research has shown that only the parent compounds have affinity to the estrogen receptors, suggesting that the pharmacokinetic behavior of bisphenols (BPs) can influence their potency...
July 2018: Environmental Health Perspectives
Huizi Li, Yinghua Liu, Xinsheng Zhang, Qing Xu, Yong Zhang, Changyong Xue, Changjiang Guo
Background: Bile acids play a pivotal role in cholesterol metabolism via the enterohepatic circulation. This study investigated the effects of medium-chain triglycerides (MCTs)/medium-chain fatty acids (MCFAs) on the reduction of bile acid absorption in the small intestine and the mechanisms of action in vivo and partially verified in vitro. Methods: Thirty-six C57BL/6 J mice with hypercholesterolaemia were randomly divided into 3 groups: fed a cholesterol-rich diet (CR group), fed a cholesterol-rich and medium-chain triglyceride diet (CR-MCT group) and fed a cholesterol-rich and long-chain triglyceride diet (CR-LCT group)...
2018: Nutrition & Metabolism
Sangwon Byun, Dong-Hyun Kim, Daniel Ryerson, Young-Chae Kim, Hao Sun, Bo Kong, Peter Yau, Grace Guo, H Eric Xu, Byron Kemper, Jongsook Kim Kemper
Farnesoid-X-Receptor (FXR) plays a central role in maintaining bile acid (BA) homeostasis by transcriptional control of numerous enterohepatic genes, including intestinal FGF19, a hormone that strongly represses hepatic BA synthesis. How activation of the FGF19 receptor at the membrane is transmitted to the nucleus for transcriptional regulation of BA levels and whether FGF19 signaling posttranslationally modulates FXR function remain largely unknown. Here we show that FXR is phosphorylated at Y67 by non-receptor tyrosine kinase, Src, in response to postprandial FGF19, which is critical for its nuclear localization and transcriptional regulation of BA levels...
July 3, 2018: Nature Communications
Amani Al-Khaifi, Sara Straniero, Veronika Voronova, Dina Chernikova, Victor Sokolov, Chanchal Kumar, Bo Angelin, Mats Rudling
BACKGROUND AND OBJECTIVES: Bile acids (BAs) traversing the enterohepatic circulation (EHC) influence important metabolic pathways. By determining individual serum BAs in relation to markers of metabolic activity, we explored how diurnal variations in their EHC relate to hepatic metabolism in normal humans. METHODS: Serum BAs, fibroblast growth factor 19 (FGF19), lipoproteins, glucose/insulin, and markers of cholesterol and BA syntheses were monitored for 32 hours in 8 healthy males...
July 2, 2018: Journal of Internal Medicine
Emmanuel Somm, Hugues Henry, Stephen J Bruce, Nicolas Bonnet, Sophie A Montandon, Nicolas J Niederländer, Andrea Messina, Sébastien Aeby, Marta Rosikiewicz, Lluis Fajas, Christine Sempoux, Serge L Ferrari, Gilbert Greub, Nelly Pitteloud
β-Klotho (encoded by Klb) is an obligate co-receptor mediating both fibroblast growth factor (FGF)15 and FGF21 signaling. Klb-/- mice are refractory to metabolic FGF15 and FGF21 action and exhibit derepressed (increased) bile acid (BA) synthesis. Here, we deeply phenotyped male Klb-/- mice on a pure C57BL/6J genetic background fed a chow diet, focusing on metabolic aspects. This aims to better understand the physiological consequences of concomitant FGF15 and FGF21 signaling deficiency, in particular on the gut-liver axis...
June 26, 2018: American Journal of Physiology. Endocrinology and Metabolism
Annemieke Smet, Koji Yahara, Mirko Rossi, Alfred Tay, Steffen Backert, Ensser Armin, James G Fox, Bram Flahou, Richard Ducatelle, Freddy Haesebrouck, Jukka Corander
Since the discovery of the human pathogen Helicobacter pylori, various other Helicobacter species have been identified in the stomach of domesticated and wild mammals. To better understand the evolutionary history of these ecologically similar but genetically distinct species, we analyzed 108 gastric Helicobacter genomes and included 54 enterohepatic Helicobacter genomes for comparison purposes. An admixture analysis supported the presence of an ecological barrier, preventing the genetic exchange between the gastric and enterohepatic Helicobacter species, and unraveled many gene flow events within and across species residing in the stomach...
June 25, 2018: ISME Journal
Courtney B Ferrebee, Jianing Li, Jamie Haywood, Kimberly Pachura, Brian S Robinson, Benjamin H Hinrichs, Rheinallt M Jones, Anuradha Rao, Paul A Dawson
Background & Aims: Ileal bile acid absorption is mediated by uptake via the apical sodium-dependent bile acid transporter (ASBT), and export via the basolateral heteromeric organic solute transporter α-β (OSTα-OSTβ). In this study, we investigated the cytotoxic effects of enterocyte bile acid stasis in Ostα -/- mice, including the temporal relationship between intestinal injury and initiation of the enterohepatic circulation of bile acids. Methods: Ileal tissue morphometry, histology, markers of cell proliferation, gene, and protein expression were analyzed in male and female wild-type and Ostα -/- mice at postnatal days 5, 10, 15, 20, and 30...
2018: Cellular and Molecular Gastroenterology and Hepatology
Magnus Simrén, Jan Tack
Functional bowel disorders (FBDs) are a spectrum of disorders characterized by combinations of symptoms attributable to the lower gastrointestinal tract. Most current first-line therapies for IBS and other FBDs target the predominant symptom and mainly affect one symptom in the symptom complex. Additional broadly effective treatment alternatives targeting the entire symptom complex are needed. New drugs for FBDs (such as lubiprostone, linaclotide, plecanatide, prucalopride, eluxadoline and rifaximin) target key mechanisms in the pathophysiology of these disorders and improve both the abnormal bowel habit and other key symptoms, such as abdominal pain and bloating...
June 21, 2018: Nature Reviews. Gastroenterology & Hepatology
Alexander L Ticho, Hyunjin Lee, Ravinder K Gill, Pradeep K Dudeja, Seema Saksena, Daesung Lee, Waddah A Alrefai
Bile acid transporters including the ileal apical sodium-dependent bile acid transporter (ASBT) and the hepatic sodium-taurocholate co-transporting polypeptide (NTCP) are crucial for the enterohepatic circulation of bile acids. Our objective was to develop a method for measuring bile acid transporter activity in real time to precisely evaluate rapid changes in their function. We designed a reporter system relying on a novel probe: cholic acid attached to luciferin via a disulfide-containing, self-immolating linker (CA-SS-Luc)...
June 21, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Sisheng Wu, Ting Luo, Siyu Wang, Jicong Zhou, Yingchun Ni, Zhengwei Fu, Yuanxiang Jin
Propamocarb (PM) is a widely used fungicide that affects lipid biosynthesis in fungi. In this study, we explored the effects of PM on mouse metabolism and gut microbiota-related pathways by exposing C57BL/6J mice to 1, 3, and 10 mg/L PM through drinking water for a duration of 10 weeks. We found that hepatic bile acids (BAs) were considerably increased in the PM-treated group. The transcription of genes related to BA synthesis and transportation were also markedly altered in the liver and the ileum; accordingly, serous BA profiles were changed...
November 15, 2018: Science of the Total Environment
Matthew Lindeblad, Alexander Lyubimov, Richard van Breemen, Kamil Gierszal, Guy Weinberg, Israel Rubinstein, Douglas L Feinstein
Patients exposed to long acting anticoagulant rodenticides (LAARs) are typically administered large amounts of oral vitamin K1 (VK1) to counteract life-threatening anti-coagulant effects. While VK1 treatment effectively prevents mortality, additional methods are needed to reduce the long duration of VK1 treatment which can last for months at high expense. We developed a model of brodifacoum (BDF) poisoning, one of the most potent LAARs, in adult male New Zealand White (NZW) rabbits. The LD50 for oral BDF was determined to be 192 μg/kg, similar to that calculated for adult rats...
June 12, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
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