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Cyp7a1

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https://www.readbyqxmd.com/read/27895309/hepatocyte-specific-expression-of-an-oncogenic-variant-of-%C3%AE-catenin-results-in-cholestatic-liver-disease
#1
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
#2
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
https://www.readbyqxmd.com/read/27855505/a-simple-fast-sensitive-and-robust-lc-ms-ms-bioanalytical-assay-for-evaluating-7%C3%AE-hydroxy-4-cholesten-3-one-biomarker-in-a-clinical-program
#3
Long Yuan, Yi Luo, Hamza Kandoussi, Qin C Ji
AIM: Serum 7α-hydroxy-cholesten-3-one (C4) has been reported as a biomarker to assess CYP7A1 enzyme activity and bile acid synthesis. To support a clinical program, a sensitive and reliable assay without derivatization was required for the analysis of C4 in human serum. Methodology & results: A systematic approach was used to optimize mass spectrometry, LC and sample extraction conditions, therefore, significantly improved assay sensitivity, and achieved the required quantification limit without derivatization...
December 2016: Bioanalysis
https://www.readbyqxmd.com/read/27845788/effects-of-pomegranate-peel-polyphenols-on-lipid-accumulation-and-cholesterol-metabolic-transformation-in-l-02-human-hepatic-cells-via-the-ppar%C3%AE-abca1-cyp7a1-pathway
#4
Ou Lv, Lifang Wang, Jianke Li, Qianqian Ma, Wei Zhao
To study the effect of pomegranate peel polyphenols on lipid accumulation and cholesterol metabolic transformation in human hepatic cells, purified pomegranate peel polyphenols (PPPs), their main component, punicalagin (PC), and the metabolite of PC, pomegranate ellagic acid (PEA), were chosen as the polyphenols to be tested. At the same time the human hepatocyte cell line L-02 was selected as the experimental cell and a model of steatotic L-02 hepatocytes in vitro was constructed in this paper. The results showed that PPPs, PC and PEA in different concentrations could decrease the total cholesterol (TC) content and increase the total bile acid (TBA) content, and so possess a lipid-lowering effect...
November 15, 2016: Food & Function
https://www.readbyqxmd.com/read/27789682/disrupted-murine-gut-to-human-liver-signaling-alters-bile-acid-homeostasis-in-humanized-mouse-liver-models
#5
Edwin C Y Chow, Holly P Quach, Yueping Zhang, Jason Z Y Wang, David C Evan, Albert P Li, Jose Silva, Rommel G Tirona, Yurong Lai, K Sandy Pang
The humanized liver mouse model is increasingly being exploited for human drug metabolism studies. However, its model stability, inter-communication between human hepatocytes and mouse non-parenchymal cells in liver and murine intestine, and changes in extrahepatic transporter and enzyme expression has not been investigated. We examined these issues in FRGN [Fah(-/-), Rag2(-/-), and IL-2rg(-/-) on NOD background] and chimeric mice: mFRGN, and hFRGN (repopulated with mouse or human hepatocytes, respectively)...
October 27, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27763549/maternal-betaine-supplementation-throughout-gestation-and-lactation-modifies-hepatic-cholesterol-metabolic-genes-in-weaning-piglets-via-ampk-lxr-mediated-pathway-and-histone-modification
#6
Demin Cai, Mengjie Yuan, Haoyu Liu, Shifeng Pan, Wenqiang Ma, Jian Hong, Ruqian Zhao
Betaine serves as an animal and human nutrient which has been heavily investigated in glucose and lipid metabolic regulation, yet the underlying mechanisms are still elusive. In this study, feeding sows with betaine-supplemented diets during pregnancy and lactation increased cholesterol content and low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI) gene expression, but decreasing bile acids content and cholesterol-7a-hydroxylase (CYP7a1) expression in the liver of weaning piglets...
October 18, 2016: Nutrients
https://www.readbyqxmd.com/read/27756364/dose-response-effect-of-berberine-on-bile-acid-profile-and-gut-microbiota-in-mice
#7
Ying Guo, YouCai Zhang, WeiHua Huang, Felcy Pavithra Selwyn, Curtis D Klaassen
BACKGROUND: Berberine (BBR) is a traditional antimicrobial herbal medicine. Recently, BBR has gained popularity as a supplement to lower blood lipids, cholesterol and glucose. Bile acids (BAs) are known to regulate blood levels of triglycerides, cholesterol, glucose and energy homeostasis, and gut flora play an important role in BA metabolism. However, whether BBR alters BAs metabolism or dose-response effect of BBR on gut flora is unknown. METHODS: In this study, the effects of various doses of BBR on the concentrations of BAs in liver and serum of male C57BL/6 mice were determined by UPLC-MS/MS, and the expression of BA-related genes, as well as the amount of 32 of the most abundant gut bacterial species in the terminal ileum and large intestine of male C57BL/6 mice were quantified by RT-PCR and Quantigene 2...
October 18, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27751910/transcriptome-profiling-of-equine-vitamin-e-deficient-neuroaxonal-dystrophy-identifies-upregulation-of-liver-x-receptor-target-genes
#8
Carrie J Finno, Matthew H Bordbari, Stephanie J Valberg, David Lee, Josi Herron, Kelly Hines, Tamer Monsour, Erica Scott, Danika L Bannasch, James Mickelson, Libin Xu
Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are not present with eNAD and the molecular basis remains unknown. Given the neuropathologic phenotypic similarity of the conditions, we assessed the molecular basis of eNAD by global transcriptome sequencing of the cervical spinal cord...
October 15, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27735997/cholesterol-lowering-effects-and-mechanisms-in-view-of-bile-acid-pathway-of-resveratrol-and-resveratrol-glucuronides
#9
Dongyan Shao, Yilin Wang, Qingsheng Huang, Junling Shi, Hui Yang, Zhongli Pan, Mingliang Jin, Haobin Zhao, Xiaoguang Xu
Resveratrol (Res) was previously reported to be capable of lowering plasma TC and LDL-C. The mechanism behind Res is not clearly understood, although it is presumed to have an effect on bile acid metabolism in the liver: a significant way in eliminating cholesterol from the body. As one of the major metabolites of Res in the liver, resveratrol glucuronides (Gres) is suspected to also contribute to the overall cholestrol-lowering activity of Res, which needs to be studied. In this research, when HepG2 steatosis hepatic cells were treated with Res and Gres at different concentration levels, Res and Gres showed similar activity in lowering cellular TC content...
October 13, 2016: Journal of Food Science
https://www.readbyqxmd.com/read/27713083/the-antihypercholesterolemic-effect-of-columbamine-from-rhizoma-coptidis-in-hfhc-diet-induced-hamsters-through-hnf-4%C3%AE-ftf-mediated-cyp7a1-activation
#10
Yue Wang, Yulong Han, Fangni Chai, Hongmei Xiang, Tao Huang, Shuming Kou, Bing Han, Xiaobao Gong, Xiaoli Ye
The aim of this study was to investigate the antihypercholesterolemic activity and potential molecular mechanism of columbamine (COL) that was prepared by extraction from Rhizoma Coptidis in hamsters and HepG2 cells. The results displayed that the COL from Rhizoma Coptidis was a safe natural compound with a LD50 0f 1524.6mg/kg and no detectable toxic symptoms during the observation of chronic toxicity. COL dose-dependently reversed the abnormal lipid levels induced by HFHC diet. Specifically, COL(M) and COL(H) significantly reduced the blood lipid levels(TC, TG and LDL-c) and enhanced the fecal contents of TBA by 21...
October 3, 2016: Fitoterapia
https://www.readbyqxmd.com/read/27698957/corn-silk-extract-improves-cholesterol-metabolism-in-c57bl-6j-mouse-fed-high-fat-diets
#11
Jae Hoon Cha, Sun Rim Kim, Hyun Joong Kang, Myung Hwan Kim, Ae Wha Ha, Woo Kyoung Kim
BACKGROUND/OBJECTIVES: Corn silk (CS) extract contains large amounts of maysin, which is a major flavonoid in CS. However, studies regarding the effect of CS extract on cholesterol metabolism is limited. Therefore, the purpose of this study was to determine the effect of CS extract on cholesterol metabolism in C57BL/6J mouse fed high-fat diets. MATERIALS/METHODS: Normal-fat group fed 7% fat diet, high-fat (HF) group fed 25% fat diet, and high-fat with corn silk (HFCS) group were orally administered CS extract (100 mg/kg body weight) daily...
October 2016: Nutrition Research and Practice
https://www.readbyqxmd.com/read/27693527/effect-of-hfd-stz-on-expression-of-genes-involved-in-lipid-cholesterol-and-glucose-metabolism-in-rats
#12
Luisa Pozzo, Andrea Vornoli, Ilaria Coppola, Clara Maria Della Croce, Lucia Giorgetti, Pier Giovanni Gervasi, Vincenzo Longo
AIMS: The aim of the study was to evaluate lipid, cholesterol and glucose metabolism in a novel rat model of non-alcoholic fatty liver disease (NAFLD). MAIN METHODS: Rats (Wistar) were fed high fat/cholesterol diet (HFD) and a single low dose (35mg/kg) of streptozotocin (STZ). Collagen and glycogen content, oxidative stress and glucokinase activity were measured using biochemical assays. Other metabolic pathway were assessed by qRT-PCR. KEY FINDINGS: HFD/STZ treated rats, compared to control ones, showed an increase in expression of biomarkers of inflammation (TNFα, IL6), fibrosis (TGFβ), mitochondrial stress (UCP2) and oxidative stress (GSH and carbonylated proteins) but not of ER stress (CHOP, XBP1)...
September 28, 2016: Life Sciences
https://www.readbyqxmd.com/read/27651393/evolution-of-digestive-enzymes-and-rnase1-provides-insights-into-dietary-switch-of-cetaceans
#13
Zhengfei Wang, Shixia Xu, Kexing Du, Fang Huang, Zhuo Chen, Kaiya Zhou, Wenhua Ren, Guang Yang
Although cetaceans (whales, porpoises, and dolphins) have multi-chambered stomachs, feeding habits of modern cetaceans have dramatically changed from herbivorous to carnivorous. However, the genetic basis underlying this dietary switch remains unexplored. Here, we present the first systematic investigation of 10 digestive enzymes genes (i.e., CYP7A1, CTRC, LIPC, LIPF, PNLIP, PGC, PRSS1, SI, SLC5A1, and TMPRSS15) of representative cetaceans, and the evolutionary trajectory of RNASE1 in cetartiodactylans. Positive selections were detected with proteinases (i...
December 2016: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/27639250/sirtuin-1-activation-alleviates-cholestatic-liver-injury-in-a-cholic-acid-fed-mouse-model-of-cholestasis
#14
Supriya R Kulkarni, Carol J Soroka, Lee R Hagey, James L Boyer
: Sirtuin1 (Sirt1; mammalian homolog of Saccharomyces cerevisiae enzyme Sir2) is a transcriptional and transactivational regulator of murine farnesoid X receptor (Fxr), which is the primary bile acid (BA) sensor, and critical regulator of BA metabolism in physiological and pathophysiological conditions. Previous studies have suggested compromised Sirt1 expression in rodent models of cholestatic liver injury. We hypothesized that Sirt1 could be potentially targeted to alleviate cholestatic liver injury...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27632016/dietary-silymarin-supplementation-promotes-growth-performance-and-improves-lipid-metabolism-and-health-status-in-grass-carp-ctenopharyngodon-idellus-fed-diets-with-elevated-lipid-levels
#15
Peizhen Xiao, Hong Ji, Yuantu Ye, Baotong Zhang, Yongsheng Chen, Jingjing Tian, Pin Liu, Liqiao Chen, Zhenyu Du
This study was carried out to evaluate whether silymarin supplementation influences growth, lipid metabolism, and health status in grass carp fed elevated dietary lipid levels. The juvenile fish (27.43 ± 0.17 g/tail) were fed six isonitrogenous and isocaloric diets in a factorial design containing 0, 100, or 200 mg kg(-1) silymarin (SM0, SM100, SM200) associated with either 4 or 8 % lipid level (low lipid, LL, and high lipid, HL, respectively) for 82 days. The results showed that both dietary silymarin supplementation and high lipid level significantly enhanced growth performance (WG, SGR), protein efficiency ratio, and feed utilization...
September 8, 2016: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/27629819/simvastatin-promotes-npc1-mediated-free-cholesterol-efflux-from-lysosomes-through-cyp7a1-lxr%C3%AE-signalling-pathway-in-oxldl-loaded-macrophages
#16
Xiaoyang Xu, Aolin Zhang, Matthew S Halquist, Xinxu Yuan, Scott C Henderson, William L Dewey, Pin-Lan Li, Ningjun Li, Fan Zhang
Statins, 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors, are the first-line medications prescribed for the prevention and treatment of coronary artery diseases. The efficacy of statins has been attributed not only to their systemic cholesterol-lowering actions but also to their pleiotropic effects that are unrelated to cholesterol reduction. These pleiotropic effects have been increasingly recognized as essential in statins therapy. This study was designed to investigate the pleiotropic actions of simvastatin, one of the most commonly prescribed statins, on macrophage cholesterol homeostasis with a focus on lysosomal free cholesterol egression...
September 15, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27609522/restoration-of-enterohepatic-bile-acid-pathways-in-pregnant-mice-following-short-term-activation-of-fxr-by-gw4064
#17
Jamie E Moscovitz, Bo Kong, Kyle Buckley, Brian Buckley, Grace L Guo, Lauren M Aleksunes
The farnesoid X receptor (Fxr) controls bile acid homeostasis by coordinately regulating the expression of synthesizing enzymes (Cyp7a1, Cyp8b1), conjugating enzymes (Bal, Baat) and transporters in the ileum (Asbt, Ostα/β) and liver (Ntcp, Bsep, Ostβ). Transcriptional regulation by Fxr can be direct, or through the ileal Fgf15/FGF19 and hepatic Shp pathways. Circulating bile acids are increased during pregnancy due to hormone-mediated disruption of Fxr signaling. While this adaptation enhances lipid absorption, elevated bile acids may predispose women to develop maternal cholestasis...
November 1, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27589928/obeticholic-acid-for-the-treatment-of-primary-biliary-cirrhosis
#18
David E J Jones
INTRODUCTION: There is significant unmet need in Primary Biliary Cholangitis (PBC) in patients under-responsive to the only approved therapy Ursodeoxycholic Acid (UDCA) who are at increased risk of progressing to end-stage liver disease. Obeticholic Acid (OCA) is a farnesoid X receptor (FXR) agonist which has been evaluated as a second line therapy in PBC and has recently been licenced by the FDA. AREAS COVERED: The pharmacology and biology of OCA as an FXR agonist and its clinical benefits...
September 2, 2016: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27570155/quantitative-metabolomic-profiling-of-plasma-urine-and-liver-extracts-by-1-h-nmr-spectroscopy-characterizes-different-stages-of-atherosclerosis-in-hamsters
#19
Wei Guo, Chunying Jiang, Liu Yang, Tianqi Li, Xia Liu, Mengxia Jin, Kai Qu, Huili Chen, Xiangju Jin, Hongyue Liu, Haibo Zhu, Yinghong Wang
Atherosclerosis (AS) is a progressive disease that contributes to cardiovascular disease and shows a complex etiology, including genetic and environmental factors. To understand systemic metabolic changes and to identify potential biomarkers correlated with the occurrence and perpetuation of diet-induced AS, we applied (1)H NMR-based metabolomics to detect the time-related metabolic profiles of plasma, urine, and liver extracts from male hamsters fed a high fat and high cholesterol (HFHC) diet. Conventional biochemical assays and histopathological examinations as well as protein expression analyses were performed to provide complementary information...
October 7, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27539104/the-effect-of-colesevelam-treatment-on-bile-acid-and-lipid-metabolism-and-glycemic-control-in-healthy-men
#20
T Blahová, L Peterková, M Leníček, M Vlachová, K Zemánková, V Adámková, L Vítek, J Kovář
The treatment of hypercholesterolemia with bile acid (BA) sequestrants results in upregulation of BA synthesis through the classical pathway initiated by cholesterol 7alpha-hydroxylase (CYP7A1). To characterize the detailed dynamics of serum lipid and BA concentrations and the BA synthesis rate in response to treatment with BA sequestrants and to determine whether the -203A/C promoter polymorphism of the CYP7A1 encoding gene (CYP7A1) affects such a response, this pilot study was carried out in healthy men (8 homozygous for the -203A allele and 8 homozygous for the -203C allele of CYP7A1)...
August 19, 2016: Physiological Research
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