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https://www.readbyqxmd.com/read/27904713/farnesoid-x-receptor-ligand-cdca-suppresses-human-prostate-cancer-cells-growth-by-inhibiting-lipid-metabolism-via-targeting-sterol-response-element-binding-protein-1
#1
Nian Liu, Jun Zhao, Jinguo Wang, Haolin Teng, Yaowen Fu, Hang Yuan
AIM: A wealth of studies have demonstrated that abnormal cellular lipid metabolism plays an important role in prostate cancer (PCa) development. Therefore, manipulating lipid metabolism is a potential PCa therapy strategy. In this study, our goal is to investigate the role of farnesoid X receptor (FXR) in regulating the proliferation and lipid metabolism of human PCa cells following its ligand chenodexycholic acid (CDCA) treatment. METHODS: Oil Red O was used to stain lipid contents in PCa cells, and siRNA knockdown was performed to deplete FXR expression...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27899892/age-dependent-hepatic-udp-glucuronosyltransferase-gene-expression-and-activity-in-children
#2
Elizabeth Neumann, Huma Mehboob, Jacqueline Ramírez, Snezana Mirkov, Min Zhang, Wanqing Liu
UDP-glucuronosyltransferases (UGTs) are important phase II drug metabolism enzymes. The aim of this study was to explore the relationship between age and changes in mRNA expression and activity of major human hepatic UGTs, as well as to understand the potential regulatory mechanism underlying this relationship. Using previously generated data, we investigated age-dependent mRNA expression levels of 11 hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B10, UGT2B15, and UGT2B17) and 16 transcription factors (AHR, AR, CAR, ESR2, FXR, GCCR, HNF1a, HNF3a, HNF3b, HNF4a, PPARA, PPARG, PPARGC, PXR, SP1, and STAT3) in liver tissue of donors (n = 38) ranging from 0 to 25 years of age...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27896916/dihydroartemisinin-counteracts-fibrotic-portal-hypertension-via-farnesoid-x-receptor-dependent-inhibition-of-hepatic-stellate-cell-contraction
#3
Wenxuan Xu, Chunfeng Lu, Feng Zhang, Jiangjuan Shao, Shunyu Yao, Shizhong Zheng
Portal hypertension is a frequent pathological symptom occurring especially in hepatic fibrosis and cirrhosis. Current paradigms indicate that inhibition of hepatic stellate cell (HSC) activation and contraction is anticipated to be an attractive therapeutic strategy, because activated HSC dominantly facilitates an increase in intrahepatic vein pressure through secreting extracellular matrix and contracting. Our previous in vitro study indicated that dihydroartemisinin (DHA) inhibited contractility of cultured HSC by activating intracellular farnesoid X receptor (FXR)...
November 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27895309/hepatocyte-specific-expression-of-an-oncogenic-variant-of-%C3%AE-catenin-results-in-cholestatic-liver-disease
#4
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/27880978/defining-the-relationship-between-farsenoid-x-receptor-hepatitis-b-virus-x-protein-and-hcc-it-s-complicated
#5
EDITORIAL
Lindsey Kennedy, Heather Francis
The relationship between hepatitis B virus X protein (HBx), farsenoid X receptor (FXR) and hepatocellular carcinoma (HCC) is a complicated one in that we have a viral protein interaction that can drive tumorigenesis or inhibit HCC depending upon transactivation of full-length or truncated HBx. In the current article the authors have elegantly described a system of HBx-FXR interaction that demonstrates inhibition of HCC tumor growth via activation of full-length HBx. The paper employs both in vivo and in vitro studies including using FXR knockout mice crossed with HBx induced mice...
November 23, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27871908/acetylated-deoxycholic-dca-and-cholic-ca-acids-are-potent-ligands-of-pregnane-x-pxr-receptor
#6
Alejandro Carazo, Lucie Hyrsova, Jan Dusek, Hana Chodounska, Alzbeta Horvatova, Karel Berka, Vaclav Bazgier, Hongying Gan-Schreier, Waleé Chamulitrat, Eva Kudova, Petr Pavek
The Pregnane X (PXR), Vitamin D (VDR) and Farnesoid X (FXR) nuclear receptors have been shown to be receptors of bile acids controlling their detoxification or synthesis. Chenodeoxycholic (CDCA) and lithocholic (LCA) acids are ligands of FXR and VDR, respectively, whereas 3-keto and acetylated derivates of LCA have been described as ligands for all three receptors. In this study, we hypothesized that oxidation or acetylation at position 3, 7 and 12 of bile acids DCA (deoxycholic acid), LCA, CA (cholic acid), and CDCA by detoxification enzymes or microbiome may have an effect on the interactions with bile acid nuclear receptors...
November 18, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27871799/molecular-mechanisms-of-pfoa-induced-toxicity-in-animals-and-humans-implications-for-health-risks
#7
REVIEW
Kan Li, Peng Gao, Ping Xiang, Xuxiang Zhang, Xinyi Cui, Lena Q Ma
As an emerging persistent organic pollutant (POP), perfluorooctanoate (PFOA) is one of the most abundant perfluorinated compounds (PFCs) in the environment. This review summarized the molecular mechanisms and signaling pathways of PFOA-induced toxicity in animals and humans as well as their implications for health risks in humans. Traditional PFOA-induced signal pathways such as peroxisome proliferating receptor alpha (PPARα), constitutive androstane receptor (CAR), farnesoid X receptor (FXR), and pregnane-X receptor (PXR) may not be important for PFOA-induced health effects on humans...
November 18, 2016: Environment International
https://www.readbyqxmd.com/read/27865854/obeticholic-acid-protects-against-carbon-tetrachloride-induced-acute-liver-injury-and-inflammation
#8
Da-Gang Zhang, Cheng Zhang, Jun-Xian Wang, Bi-Wei Wang, Hua Wang, Zhi-Hui Zhang, Yuan-Hua Chen, Yan Lu, Li Tao, Jian-Qing Wang, Xi Chen, De-Xiang Xu
The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl4)-induced acute liver injury. Mice were intraperitoneally injected with CCl4 (0.15ml/kg). In CCl4+OCA group, mice were orally with OCA (5mg/kg) 48, 24 and 1h before CCl4. As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl4-induced elevation of serum ALT and hepatic necrosis...
November 16, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27853248/activation-of-fxr-protects-against-renal-fibrosis-via-suppressing-smad3-expression
#9
Kai Zhao, Jialin He, Yan Zhang, Zhizhen Xu, Haojun Xiong, Rujun Gong, Song Li, Shan Chen, Fengtian He
Renal fibrosis is the common pathway of most chronic kidney disease progression to end-stage renal failure. The nuclear receptor FXR (farnesoid X receptor), a multiple functional transcription factor, plays an important role in protecting against fibrosis. The TGFβ-Smad signaling has a central role in kidney fibrosis. However, it remains unclear whether FXR plays direct anti-fibrotic effect in renal fibrosis via regulating TGFβ-Smad pathway. In this study, we found that the level of FXR was negatively correlated with that of Smad3 and fibronectin (a marker of fibrosis) in human fibrotic kidneys...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27846919/intestinal-bile-acid-receptors-are-key-regulators-of-glucose-homeostasis
#10
Mohamed-Sami Trabelsi, Sophie Lestavel, Bart Staels, Xavier Collet
In addition to their well-known function as dietary lipid detergents, bile acids have emerged as important signalling molecules that regulate energy homeostasis. Recent studies have highlighted that disrupted bile acid metabolism is associated with metabolism disorders such as dyslipidaemia, intestinal chronic inflammatory diseases and obesity. In particular, type 2 diabetes (T2D) is associated with quantitative and qualitative modifications in bile acid metabolism. Bile acids bind and modulate the activity of transmembrane and nuclear receptors (NR)...
November 16, 2016: Proceedings of the Nutrition Society
https://www.readbyqxmd.com/read/27822554/farnesoid-x-receptor-signaling-shapes-the-gut-microbiota-and-controls-hepatic-lipid-metabolism
#11
Limin Zhang, Cen Xie, Robert G Nichols, Siu H J Chan, Changtao Jiang, Ruixin Hao, Philip B Smith, Jingwei Cai, Margaret N Simons, Emmanuel Hatzakis, Costas D Maranas, Frank J Gonzalez, Andrew D Patterson
The gut microbiota modulates obesity and associated metabolic phenotypes in part through intestinal farnesoid X receptor (FXR) signaling. Glycine-β-muricholic acid (Gly-MCA), an intestinal FXR antagonist, has been reported to prevent or reverse high-fat diet (HFD)-induced and genetic obesity, insulin resistance, and fatty liver; however, the mechanism by which these phenotypes are improved is not fully understood. The current study investigated the influence of FXR activity on the gut microbiota community structure and function and its impact on hepatic lipid metabolism...
September 2016: MSystems
https://www.readbyqxmd.com/read/27821667/obeticholic-acid-protects-against-lipopolysaccharide-induced-fetal-death-and-intrauterine-growth-restriction-through-its-anti-inflammatory-activity
#12
Yuan-Hua Chen, Xiao-Guang Hu, Yan Zhou, Zhen Yu, Lin Fu, Gui-Bin Zhang, Qing-Li Bo, Hua Wang, Cheng Zhang, De-Xiang Xu
Farnesoid X receptor (FXR) is expressed in human and rodent placentas. Nevertheless, its function remains obscure. This study investigated the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, on LPS-induced fetal death and intrauterine growth restriction. All pregnant mice except controls were i.p. injected with LPS (100 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were orally administered with OCA (5 mg/kg) daily from GD13 to GD17. As expected, placental FXR signaling was activated by OCA...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27818587/improved-glucose-metabolism-following-bariatric-surgery-is-associated-with-increased-circulating-bile-acid-concentrations-and-remodeling-of-the-gut-microbiome
#13
REVIEW
Lukasz Kaska, Tomasz Sledzinski, Agnieszka Chomiczewska, Agnieszka Dettlaff-Pokora, Julian Swierczynski
Clinical studies have indicated that circulating bile acid (BA) concentrations increase following bariatric surgery, especially following malabsorptive procedures such as Roux-en-Y gastric bypasses (RYGB). Moreover, total circulating BA concentrations in patients following RYGB are positively correlated with serum glucagon-like peptide-1 concentrations and inversely correlated with postprandial glucose concentrations. Overall, these data suggest that the increased circulating BA concentrations following bariatric surgery - independently of calorie restriction and body-weight loss - could contribute, at least in part, to improvements in insulin sensitivity, incretin hormone secretion, and postprandial glycemia, leading to the remission of type-2 diabetes (T2DM)...
October 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27818225/protective-effects-of-srt1720-via-the-hnf1%C3%AE-fxr-signalling-pathway-and-anti-inflammatory-mechanisms-in-mice-with-estrogen-induced-cholestatic-liver-injury
#14
Linxi Yu, Xiaoxin Liu, Xiaojiaoyang Li, Zihang Yuan, Hang Yang, Luyong Zhang, Zhenzhou Jiang
Sirtuin 1 (SIRT1) is the most conserved mammalian NAD(+)-dependent protein deacetylase and is a member of the silent information regulator 2 (Sir2) families of proteins (also known as Sirtuins). In the liver, hepatic SIRT1 modulates bile acid metabolism through the regulation of farnesoid X receptor (FXR) expression. FXR is one of the most important nuclear receptors involved in the regulation of bile acid metabolism. SIRT1 modulates the FXR expression at multiple levels, including direct deacetylation of this transcription factor and transcriptional regulation through hepatocyte nuclear factor 1α (HNF1α)...
November 3, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27808040/endobarrier-gastrointestinal-liner-delineation-of-underlying-mechanisms-and-clinical-effects
#15
Ulrich Rohde
Bariatric surgery (e.g. Roux-en-Y gastric bypass (RYGB)) has proven the most effective way of achieving sustainable weight losses and remission of type 2 diabetes (T2D). Studies indicate that the effectiveness of RYGB is mediated by an altered gastrointestinal tract anatomy, which in particular favours release of the gut incretin hormone glucagon-like peptide-1 (GLP-1). The EndoBarrier gastrointestinal liner or duodenal-jejunal bypass sleeve (DJBS) is an endoscopic deployable minimally invasive and fully reversible technique designed to mimic the bypass component of the RYGB...
November 2016: Danish Medical Journal
https://www.readbyqxmd.com/read/27789682/disrupted-murine-gut-to-human-liver-signaling-alters-bile-acid-homeostasis-in-humanized-mouse-liver-models
#16
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/27787720/antifibrotic-effect-of-total-flavonoids-of-astmgali-radix-on-dimethylnitrosamine-induced-liver-cirrhosis-in-rats
#17
Yang Cheng, Jing-Yin Mai, Mei-Feng Wang, Gao-Feng Chen, Jian Ping
OBJECTIVE: To study the effect of total flavonoids of Astmgali Radix (TFA) on liver cirrhosis induced with dimethylnitrosamine (DMN) in rats, and the effect on peroxisome proliferator-activated receptor γ (PPARγ), uncoupling protein 2 (UCP2) and farnesoid X receptor (FXR). METHODS: Fifty-three Sprague-Dawley rats were randomly divided into a control group (10 rats) and a DMN group (43 rats). Rats in the DMN group were given DMN for 4 weeks and divided randomly into a model group (14 rats), a low-dosage TFA group (14 rats) and a high-dosage TFA group (15 rats) in the 3rd week...
October 27, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27777632/the-effect-of-maternal-undernutrition-on-the-rat-placental-transcriptome-protein-restriction-up-regulates-cholesterol-transport
#18
Zoe Daniel, Angelina Swali, Richard Emes, Simon C Langley-Evans
BACKGROUND: Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences. METHODS: Pregnant rats were fed control or a low protein diet from conception to day 13 gestation...
2016: Genes & Nutrition
https://www.readbyqxmd.com/read/27774647/bile-acid-excess-induces-cardiomyopathy-and-metabolic-dysfunctions-in-the-heart
#19
Moreshwar Desai, Bhoomika Mathur, Zeena Eblimit, Hernan Vasquez, Heinrich Taegtmeyer, Saul Karpen, Daniel J Penny, David D Moore, Sayeepriyadarshini Anakk
: Cardiac dysfunction in patients with liver cirrhosis is strongly associated with increased serum bile acid concentrations. Here we show that excess bile acids decrease fatty acid oxidation in cardiomyocytes and can cause heart dysfunction, a cardiac syndrome that we term Cholecardia. Fxr; Shp double knockout (DKO) mice, a model for bile acid overload, display cardiac hypertrophy, bradycardia, and exercise intolerance. In addition, DKO mice exhibit an impaired cardiac response to catecholamine challenge...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27773935/alisol-b-23-acetate-protects-against-non-alcoholic-steatohepatitis-in-mice-via-farnesoid-x-receptor-activation
#20
Qiang Meng, Xing-Ping Duan, Chang-Yuan Wang, Zhi-Hao Liu, Peng-Yuan Sun, Xiao-Kui Huo, Hui-Jun Sun, Jin-Yong Peng, Ke-Xin Liu
AIM: Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from the traditional Chinese medicine rhizoma alismatis, which exhibits a number of pharmacological activities, including anti-hepatitis virus, anti-cancer and antibacterial effects. In this study we examined whether AB23A protected against non-alcoholic steatohepatitis (NASH) in mice, and the mechanisms underlying the protective effects. METHODS: NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4 weeks...
October 24, 2016: Acta Pharmacologica Sinica
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