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https://www.readbyqxmd.com/read/28067465/cholestyramine-alters%C3%A2-bile-acid%C3%A2-amounts-and-the-expression-of-cholesterol-related-genes-in-rabbit-intestinal-and-hepatic-tissues
#1
Dong Ni Qiu, Quan Shang, Da Yu Sun, Wei Qun Ding, Zhong Guang Luo, Jian Chen, Wei Ru Jiang, Jian Ping Huang, Xiao Yun Jiang
OBJECTIVE: Cholestyramine, as a bile acid sequestering exchange resin, has been wildly used to treat hypercholesterolemia. The aim of this study was to explore how cholestyramine regulated serum cholesterol amounts and bile acid levels in animal models. METHODS: The New Zealand White rabbits were randomly assigned to the control (given distilled water) and cholestyramine (CHO)-treated (given cholestyramine 1 g/kg/day for 2 weeks) groups. To assess bile acid pool size, bile fistulas were generated in five rabbits in each group...
January 9, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28056490/knockout-of-the-primary-sclerosing-cholangitis-risk-gene-fut2-causes-liver-disease-in-mice
#2
Luca Maroni, Simon D Hohenester, Stan F J van de Graaf, Dagmar Tolenaars, Krijn van Lienden, Joanne Verheij, Marco Marzioni, Tom H Karlsen, Ronald P J Oude Elferink, Ulrich Beuers
: The etiopathogenesis of primary sclerosing cholangitis (PSC) is unknown. Genetic variants of fucosyltransferase 2 (FUT2) have been identified in genome-wide association studies as risk factor for PSC. We investigated the role of Fut2 in murine liver pathophysiology by studying Fut2(-/-) mice. Fut2(-/-) mice were viable and fertile, had lower body weight than wild type (wt) littermates and grey fur, as described earlier. Half of the Fut2(-/-) mice showed serum bile salt levels 40 times higher than wt (Fut2(-/-)(high) ), whereas the remainder were normocholanemic (Fut2(-/-)(low) )...
January 5, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28051334/glutamine-attenuates-obstructive-cholestasis-in-rats-via-farnesoid-x-receptor-mediated-regulation-of-bsep-and-mrp2
#3
Bingli Liu, Yiming Li, Hong Ji, Hongwei Lu, Hua Li, Yakun Shi
To investigate the protective effect of glutamine (Gln) against obstructive cholestasis in association with farnesoid X receptor (FXR) activation, an obstructive cholestasis model was established in male Sprague-Dawley rats by bile duct ligation (BDL). Serum biomarkers and hematoxylin plus eosin staining were used to identify the degree of hepatic injury in the rats with obstructive cholestasis after Gln treatment. Immunohistochemistry, real-time PCR, Western blot, cultured primary rat hepatocytes with FXR knockdown, and dual-luciferase reporter assay were performed to elucidate the mechanisms underlying Gln hepatoprotection...
October 5, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28041926/chronic-over-expression-of-fibroblast-growth-factor-21-increases-bile-acid-biosynthesis-by-opposing-fgf15-19-action
#4
Jun Zhang, Jamila Gupte, Yan Gong, Jennifer Weiszmann, Yuan Zhang, Ki Jeong Lee, William G Richards, Yang Li
Pharmacological doses of fibroblast growth factor (FGF) 21 effectively normalize glucose, lipid and energy homeostasis in multiple animal models with many benefits translating to obese humans with type 2 diabetes. However, a role for FGF21 in the regulation of bile acid metabolism has not been reported. Herein, we demonstrate AAV-mediated FGF21 overexpression in mice increases liver expression of the key bile acid producing enzyme, Cyp7a1, resulting in an increased bile acid pool. Furthermore, in cholecystectomized mice, FGF21-mediated bile acid pool increase led to increased transit of bile acids into colon...
December 24, 2016: EBioMedicine
https://www.readbyqxmd.com/read/28039934/prostaglandin-e2-promotes-hepatic-bile-acid-synthesis-by-an-e-prostanoid-receptor-3-mediated-hepatocyte-nuclear-receptor-4%C3%AE-cholesterol-7%C3%AE-hydroxylase-pathway-in-mice
#5
Shuai Yan, Juan Tang, Yuyao Zhang, Yuanyang Wang, Shengkai Zuo, Yujun Shen, Qianqian Zhang, Di Chen, Yu Yu, Kai Wang, Sheng-Zhong Duan, Ying Yu
: Prostaglandin E2 (PGE2 ) is an important lipid mediator of inflammation. However, whether and how PGE2 regulates hepatic cholesterol metabolism remains unknown. We found that expression of the PGE2 receptor, E prostanoid receptor 3 (EP3) expression is remarkably increased in hepatocytes in response to hyperlipidemic stress. Hepatocyte-specific deletion of EP3 receptor (EP3(hep-/-) ) results in hypercholesterolemia and augments diet-induced atherosclerosis in low-density lipoprotein receptor knockout (Ldlr(-/-) ) mice...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28039331/hepatic-deletion-of-x-box-binding-protein-1-impairs-bile-acid-metabolism-in-mice
#6
Xiaoying Liu, Anne S Henkel, Brian E LeCuyer, Susan C Hubchak, Matthew J Schipma, Eric Zhang, Richard M Green
The unfolded protein response (UPR) is an adaptive response to endoplasmic reticulum stress and the inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1) pathway of the UPR is important in lipid metabolism. However, its role in bile acid metabolism remains unknown. We demonstrate that liver-specific Xbp1 knockout (LS-Xbp1(-/-)) mice had a 45% reduction in total bile acid pool. LS-Xbp1(-/-) mice had lower serum 7α-hydroxy-4-cholesten-3-one (C4) levels compared to Xbp1(fl/fl) mice, indicating reduced CYP7A1 synthetic activity...
December 30, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/28029505/parenteral-nutrition-dysregulates-bile-salt-homeostasis-in-a-rat-model-of-parenteral-nutrition-associated-liver-disease
#7
Kiran V K Koelfat, Frank G Schaap, Caroline M J M Hodin, Ruben G J Visschers, Björn I Svavarsson, Martin Lenicek, Ronit Shiri-Sverdlov, Kaatje Lenaerts, Steven W M Olde Damink
BACKGROUND & AIMS: Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis...
September 24, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28013406/simulated-microgravity-affects-some-biological-characteristics-of-lactobacillus-acidophilus
#8
Dongyan Shao, Linbo Yao, Muhammad Shahid Riaz, Jing Zhu, Junling Shi, Mingliang Jin, Qingsheng Huang, Hui Yang
The effects of weightlessness on enteric microorganisms have been extensively studied, but have mainly been focused on pathogens. As a major component of the microbiome of the human intestinal tract, probiotics are important to keep the host healthy. Accordingly, understanding their changes under weightlessness conditions has substantial value. This study was carried out to investigate the characteristics of Lactobacillus acidophilus, a typical probiotic for humans, under simulated microgravity (SMG) conditions...
December 24, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28009872/medium-chain-fatty-acids-reduce-serum-cholesterol-by-regulating-the-metabolism-of-bile-acid-in-c57bl-6j-mice
#9
Yinghua Liu, Yong Zhang, Xinsheng Zhang, Qing Xu, Xueyan Yang, Changyong Xue
Hypercholesterolemia is one of the important risk factors of atherosclerosis (AS). The aim of this study is to explore the effect of medium-chain fatty acids (MCFAs) on serum cholesterol levels and their mechanism of action. Hyperlipemia, as a model of abnormal lipid hypermetabolism, was established by using a high fat diet in C57BL/6J mice. Forty eight mice with dyslipidemia were randomly divided into 4 groups, 12 mice per group, including the control group, the 2% caprylic acid (C8:0)-treated group, 2% capric acid (C10:0)-treated group, and 2% oleic acid (C18:1)-treated group...
December 23, 2016: Food & Function
https://www.readbyqxmd.com/read/28008998/impaired-hepatic-adaptation-to-chronic-cholestasis-induced-by-primary-sclerosing-cholangitis
#10
Malgorzata Milkiewicz, Marta Klak, Agnieszka Kempinska-Podhorodecka, Anna Wiechowska-Kozlowska, Elzbieta Urasinska, Malgorzata Blatkiewicz, Ewa Wunsch, Elwyn Elias, Piotr Milkiewicz
Pathogenesis of primary sclerosing cholangitis (PSC) may involve impaired bile acid (BA) homeostasis. We analyzed expressions of factors mediating enterohepatic circulation of BA using ileal and colonic (ascending and sigmoid) biopsies obtained from patients with PSC with and without ulcerative colitis (UC) and explanted PSC livers. Two-fold increase of BA-activated farnesoid X receptor (FXR) protein levels were seen in ascending and sigmoid colon of PSC patients with correspondingly decreased apical sodium-dependent BA transporter (ASBT) gene expression...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27988401/geniposide-attenuates-anit-induced-cholestasis-through-regulation-of-transporters-and-enzymes-involved-in-bile-acids-homeostasis-in-rats
#11
Lingling Wang, Guixin Wu, Feihua Wu, Nan Jiang, Yining Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Geniposide (GE) is one of the major iridoid glycosides isolated from the fruit of Gardenia jasminoides Ellis that has been used to treat hepatic disorders including cholestasis. However, the underlying mechanisms for GE ameliorating the reduction in bile acids accumulation by α-naphthylisothiocyanate (ANIT) remain unclear. AIM OF THE STUDY: The purpose of this study is to characterize the efficacy of GE in regulation of bile acids uptake, synthesis, metabolism, and transport in ANIT-induced rats...
December 14, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27981592/the-ascending-pathophysiology-of-cholestatic-liver-disease
#12
REVIEW
Peter L M Jansen, Ahmed Ghallab, Nachiket Vartak, Raymond Reif, Frank G Schaap, Jochen Hampe, Jan G Hengstler
In this review we develop the argument that cholestatic liver diseases, particularly PBC and PSC, evolve over time with anatomically an ascending course of the disease process. The first and early lesions are in 'downstream' bile ducts. This eventually leads to cholestasis and this causes bile salt-mediated toxic injury of the 'upstream' liver parenchyma. Bile salts are toxic in high concentration. These concentrations are present in the canalicular network, bile ducts and gallbladder. Leakage of bile from this network and ducts could be an important driver of toxicity...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27976737/altered-systemic-bile-acid-homeostasis-contributes-to-liver-disease-in-pediatric-patients-with-intestinal-failure
#13
Yong-Tao Xiao, Yi Cao, Ke-Jun Zhou, Li-Na Lu, Wei Cai
Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27939613/pharmacotoxicology-of-clinically-relevant-concentrations-of-obeticholic-acid-in-an-organotypic-human-hepatocyte-system
#14
A Dash, R A Figler, B R Blackman, S Marukian, M S Collado, M J Lawson, S A Hoang, A J Mackey, D Manka, B K Cole, R E Feaver, A J Sanyal, B R Wamhoff
Nonalcoholic steatohepatitis (NASH) is an emerging health crisis with no approved therapies. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, shows promise in NASH trials. However, the precise mechanisms mediating OCA effects and impact on cholesterol metabolism are not fully understood. We explored the pharmaco-toxicological effects of OCA on patho-physiological pathways in hepatocytes using a previously described perfused organotypic liver system that allows culture in near-physiological insulin/glucose milieus, and exhibits drug responses at clinically-relevant concentrations...
March 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27932985/pregnane-x-receptor-pxr-mediated-gene-repression-and-cross-talk-of-pxr-with-other-nuclear-receptors-via-coactivator-interactions
#15
REVIEW
Petr Pavek
Pregnane X receptor is a ligand-activated nuclear receptor (NR) that mainly controls inducible expression of xenobiotics handling genes including biotransformation enzymes and drug transporters. Nowadays it is clear that PXR is also involved in regulation of intermediate metabolism through trans-activation and trans-repression of genes controlling glucose, lipid, cholesterol, bile acid, and bilirubin homeostasis. In these processes PXR cross-talks with other NRs. Accumulating evidence suggests that the cross-talk is often mediated by competing for common coactivators or by disruption of coactivation and activity of other transcription factors by the ligand-activated PXR...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27929393/xylobiose-an-alternative-sweetener-ameliorates-diabetes-related-metabolic-changes-by-regulating-hepatic-lipogenesis-and-mir-122a-33a-in-db-db-mice
#16
Eunjin Lim, Ji Ye Lim, Eunju Kim, Yoo-Sun Kim, Jae-Ho Shin, Pu Reum Seok, Sangwon Jung, Sang-Ho Yoo, Yuri Kim
Type 2 diabetes is a major public health concern worldwide. Xylobiose (XB) consists of two molecules of d-xylose and is a major disaccharide in xylooligosaccharides that are used as prebiotics. We hypothesized that XB could regulate diabetes-related metabolic and genetic changes via microRNA expression in db/db mice. For six weeks, C57BL/KsJ-db/db mice received 5% XB as part of the total sucrose content of their diet. XB supplementation improved glucose tolerance with reduced levels of OGTT AUC, fasting blood glucose, HbA1c, insulin, and HOMA-IR...
December 5, 2016: Nutrients
https://www.readbyqxmd.com/read/27923447/amelioration-of-non-alcoholic-fatty-liver-disease-with-npc1l1-targeted-igy-or-n-3-polyunsaturated-fatty-acids-in-mice
#17
Jin-Sik Bae, Jong-Min Park, Junghoon Lee, Byung-Chul Oh, Sang-Ho Jang, Yun Bin Lee, Young-Min Han, Chan-Young Ock, Ji-Young Cha, Ki-Baik Hahm
Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk for progression to hepatocellular carcinoma in addition to comorbidities such as cardiovascular and serious metabolic diseases; however, the current therapeutic options are limited. Based on our previous report that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can significantly ameliorate high fat diet (HFD)-induced NAFLD, we explored the therapeutic efficacy of n-3 PUFAs and N-IgY, which is a chicken egg yolk-derived IgY specific for the Niemann-Pick C1-Like 1 (NPC1L1) cholesterol transporter, on NAFLD in mice...
January 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27918728/cholesterol-metabolism-in-rabbit-blastocysts-under-maternal-diabetes
#18
S Mareike Pendzialek, Maria Schindler, Torsten Plösch, Jacqueline Gürke, Elisa Haucke, Stefanie Hecht, Bernd Fischer, Anne Navarrete Santos
In the rabbit reproductive model, maternal experimentally induced insulin-dependent diabetes mellitus (expIDD) leads to accumulation of lipid droplets in blastocysts. Cholesterol metabolism is a likely candidate to explain such metabolic changes. Therefore, in the present study we analysed maternal and embryonic cholesterol concentrations and expression of related genes in vivo (diabetic model) and in vitro (embryo culture in hyperglycaemic medium). In pregnant expIDD rabbits, the serum composition of lipoprotein subfractions was changed, with a decrease in high-density lipoprotein cholesterol and an increase in very low-density lipoprotein cholesterol; in uterine fluid, total cholesterol concentrations were elevated...
December 6, 2016: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/27895309/hepatocyte-specific-expression-of-an-oncogenic-variant-of-%C3%AE-catenin-results-in-cholestatic-liver-disease
#19
Ursula J Lemberger, Claudia Fuchs, Matthias Karer, Stefanie Haas, Tatjana Stojakovic, Christian Schöfer, Hanns-Ulrich Marschall, Fritz Wrba, Makoto M Taketo, Gerda Egger, Michael Trauner, Christoph H Österreicher
BACKGROUND: The Wnt/β-catenin signaling pathway plays a crucial role in embryonic development, tissue homeostasis, wound healing and malignant transformation in different organs including the liver. The consequences of continuous β-catenin signaling in hepatocytes remain elusive. RESULTS: Livers of Ctnnb1CA hep mice were characterized by disturbed liver architecture, proliferating cholangiocytes and biliary type of fibrosis. Serum ALT and bile acid levels were significantly increased in Ctnnb1CA hep mice...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27861428/hepatogenic-differentiation-of-human-induced-pluripotent-stem-cells-on-collagen-coated-polyethersulfone-nanofibers
#20
Maryam Mahmoodinia Maymand, Hamid Reza Soleimanpour-Lichaei, Abdolreza Ardeshirylajimi, Masoud Soleimani, Samaneh Mirzaei, Athena Hajarizadeh, Maryam Kabir Salmani
Many scientists have been fascinated with Induced pluripotent stem cells (iPSCs) for cell replacement therapies. Nanofibrous biocompatible scaffolds have been shown to promote better cell adhesion and improve stem cell differentiation. In the present study, after fabrication using electrospinning technique and surface modifications, the characteristics of Polyethersulfone (PES) nanofibers were determined by scanning electron microscopy (SEM), ATR-FTIR and MTT assay. Then, the hepatogenic potential of iPSCs was evaluated using Real-Time RT-PCR and immunocytochemistry (ICC) after culture on collagen coated polyethersulfone (PES/COL) scaffolds...
November 15, 2016: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
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