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Liver X Receptor

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https://www.readbyqxmd.com/read/28214859/farnesoid-x-receptor-in-mice-prevents-severe-liver-immunopathology-during-lymphocytic-choriomeningitis-virus-infection
#1
Nadine Honke, Namir Shaabani, Cornelia Hardt, Caroline Krings, Dieter Häussinger, Philipp A Lang, Karl S Lang, Verena Keitel
BACKGROUND: Bile acids (BAs) are steroid molecules that are synthesized in the liver. In addition to their important role as a surfactant in solubilizing lipids and promoting the absorption of lipids in the gastrointestinal tract, they act as inflammagens. The role of BAs and their receptor farnesoid X receptor (FXR) during viral infection has not been studied in detail. METHODS: By using FXR-deficient mice, we investigated the role of bile acid receptor FXR during infection with lymphocytic choriomeningitis virus (LCMV)...
January 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213512/27-hydroxycholesterol-impairs-neuronal-glucose-uptake-through-an-irap-glut4-system-dysregulation
#2
Muhammad-Al-Mustafa Ismail, Laura Mateos, Silvia Maioli, Paula Merino-Serrais, Zeina Ali, Maria Lodeiro, Eric Westman, Eran Leitersdorf, Balázs Gulyás, Lars Olof-Wahlund, Bengt Winblad, Irina Savitcheva, Ingemar Björkhem, Angel Cedazo-Mínguez
Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced (18)F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)-mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N)...
February 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28195307/effect-of-obeticholic-acid-on-liver-regeneration-following-portal-vein-embolization-in-an-experimental-model
#3
P B Olthof, F Huisman, F G Schaap, K P van Lienden, R J Bennink, R F van Golen, M Heger, J Verheij, P L Jansen, S W Olde Damink, T M van Gulik
BACKGROUND: The bile salt-activated transcription factor farnesoid X receptor (FXR) is a key mediator of proliferative bile salt signalling, which is assumed to play a role in the early phase of compensatory liver growth. The aim of this study was to evaluate the effect of a potent FXR agonist (obeticholic acid, OCA) on liver growth following portal vein embolization (PVE). METHODS: Rabbits were allocated to receive daily oral gavage with OCA (10 mg/kg) or vehicle (control group) starting 7 days before PVE (n = 18 per group), and continued until 7 days after PVE...
February 13, 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/28192885/polyphenols-rich-passiflora-leschenaultii-leaves-modulating-farnesoid-x-receptor-and-pregnane-x-receptor-against-paracetamol-induced-hepatotoxicity-in-rats
#4
Saravanan Shanmugam, Dhivya Sivaraj, Bruno Dos Santos Lima, Paula Dos Passos Menezes, Yasmim Maria Barbosa Gomes de Carvalho, Adriano Antunes de Souza Araújo, Narendra Narain, Mairim Russo Serafini, Lucindo José Quintans Júnior, Luciana Scotti, Marcus Tulius Scotti, Thangaraj Parimelazhagan
The hepatoprotective effect of P. leschenaultii. (DC) leaves was investigated in rats under paracetamol induced oxidative stress. Leaf acetone extract (200 and 400mg/kg) were administered daily via gavage for 14days before paracetamol (2000mg/kg, p.o.) treatment. After the experiment, the levels of serum biochemical parameters and enzymatic antioxidant levels were determined. Furthermore, liver tissues were analyzed histopathologically. Additionally, the molecular docking studies of the identified compounds against PXR and FXR proteins were also performed...
February 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28190475/calycosin-attenuates-triglyceride-accumulation-and-hepatic-fibrosis-in-murine-model-of-non-alcoholic-steatohepatitis-via-activating-farnesoid-x-receptor
#5
Xingping Duan, Qiang Meng, Changyuan Wang, Zhihao Liu, Qi Liu, Huijun Sun, Pengyuan Sun, Xiaobo Yang, Xiaokui Huo, Jinyong Peng, Kexin Liu
BACKGROUND: Non-alcoholic steatohepatitis (NASH) represents the more severe end of hepatic steatosis and is associated with progressive liver disease. Calycosin, derived from the root of Radix Astragali, has been demonstrated to have favorable efficacy on acute liver injury. PURPOSE: The present study was to investigate the hepatoprotective effect of calycosin on attenuating triglyceride accumulation and hepatic fibrosis, as well as explore the potential mechanism in murine model of NASH...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28187366/a-combination-of-dietary-n-3-fatty-acids-and-a-cyclooxygenase-1-inhibitor-attenuates-nonalcoholic-fatty-liver-disease-in-mice
#6
Viswanathan Saraswathi, Curtis Perriotte-Olson, Murali Ganesan, Cyrus V Desouza, Yazen Alnouti, Michael J Duryee, Geoffrey M Thiele, Tara M Nordgren, Dahn L Clemens
We sought to determine whether a combination of purified n-3 fatty acids (n-3) and SC-560 (SC), a cyclooxygenase-1-specific inhibitor, is effective in ameliorating nonalcoholic fatty liver disease in obesity. Female wild-type mice were fed a high-fat and high-cholesterol diet (HF) supplemented with n-3 in the presence or absence of SC. Mice treated with SC alone exhibited no change in liver lipids, whereas n-3-fed mice tended to have lower hepatic lipids. Mice given n-3+SC had significantly lower liver lipids compared with HF controls indicating enhanced lipid clearance...
January 27, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28178657/liver-x-receptors-agonist-gw3965-re-sensitizes-gefitinib-resistant-human-non-small-cell-lung-cancer-cell-to-gefitinib-treatment-by-inhibiting-nf-%C3%AE%C2%BAb-in-vitro
#7
Yong Hu, Jialan Zang, Haixia Cao, Ying Wu, Dali Yan, Xiaobing Qin, Leilei Zhou, Fan Fan, Jie Ni, Xiaoyue Xu, Huanhuan Sha, Siwen Liu, Shaorong Yu, Zhuo Wang, Rong Ma, Jianzhong Wu, Jifeng Feng
The recent research shows that the inhibition of the nuclear factor-κB (NF-κB) pathway is a promising therapeutic option for patients who progress after treatment with the novel mutant-selective EGFR-TKIs. For propose to find a nontoxic drug to reverse the acquired gefitinib resistance, we examined whether the Liver X Receptors agonist GW3965 affect gefitinib resistance of HCC827/GR-8-2 cells. Cell viability was measured by CCK-8 assay. Levels of NF-κB, p-AKT and caspases were detected by Western blot analysis...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178326/quantitative-liver-proteomics-identifies-fgf19-targets-that-couple-metabolism-and-proliferation
#8
Vittoria Massafra, Alexandra Milona, Harmjan R Vos, Boudewijn M T Burgering, Saskia W C van Mil
Fibroblast growth factor 19 (FGF19) is a gut-derived peptide hormone that is produced following activation of Farnesoid X Receptor (FXR). FGF19 is secreted and signals to the liver, where it contributes to the homeostasis of bile acid (BA), lipid and carbohydrate metabolism. FGF19 is a promising therapeutic target for the metabolic syndrome and cholestatic diseases, but enthusiasm for its use has been tempered by FGF19-mediated induction of proliferation and hepatocellular carcinoma. To inform future rational design of FGF19-variants, we have conducted temporal quantitative proteomic and gene expression analyses to identify FGF19-targets related to metabolism and proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28169169/drugbank-screening-revealed-alitretinoin-and-bexarotene-as-liver-x-receptor-modulators
#9
Pascal Heitel, Janosch Achenbach, Daniel Moser, Ewgenij Proschak, Daniel Merk
In silico screening of DrugBank database to detect liver X receptor (LXR) agonism of marketed drugs using a self-organizing map and successive LXR-Gal4 hybrid reporter gene assay evaluation in vitro discovered alitretinoin and bexarotene as partial liver X receptor agonists. Dose-response curves demonstrated that plasma concentrations observed in clinical trials are sufficient for LXR activation and thus could account for LXR-mediated side-effects such as hypercholesterolemia and hyperlipidemia. The discovered drugs are the first reported dual LXR/RXR agonists and can serve as lead structures for LXR and dual LXR/RXR modulator development...
January 25, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28167099/27-hydroxycholesterol-regulates-cholesterol-synthesis-and-transport-in-c6-glioma-cells
#10
Yu An, Dan-Di Zhang, Huan-Ling Yu, Wei-Wei Ma, Yan-Hui Lu, Quan-Ri Liu, Rong Xiao
The oxysterol 27-Hydroxycholesterol (27-OHC) is a major cholesterol metabolite that can cross the blood brain barrier (BBB) from peripheral circulation to the brain. Currently, the role of 27-OHC on cholesterol homeostasis in astrocytes and the underlying mechanisms are not defined. Since all brain cholesterol is essentially synthesized in brain itself and astrocytes as net producers of cholesterol are essential for normal brain function, here we investigated the effects of 27-OHC on cholesterol synthesis and transport in C6 glioma cells...
February 3, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28166197/chemerin-has-a-protective-role-in-hepatocellular-carcinoma-by-inhibiting-the-expression-of-il-6-and-gm-csf-and-mdsc-accumulation
#11
Y Lin, X Yang, W Liu, B Li, W Yin, Y Shi, R He
Hepatocellular carcinoma (HCC) is linked to inflammation and immunosuppression. Chemerin is highly expressed in the liver and implicated in the regulation of inflammation. However, the role of chemerin in HCC remains unclear. In this study, we aimed to investigate whether chemerin is able to influence HCC progression by regulating tumor-associated inflammation. Here we demonstrated that chemerin significantly decreased in blood and tumor tissues of HCC patients, and tumor chemerin levels were inversely associated with the prognosis...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28164071/transcriptional-coordination-of-hepatic-autophagy-by-nutrient-sensing-nuclear-receptor-ppar%C3%AE-and-fxr
#12
REVIEW
Jae Man Lee
Nuclear receptors are in general ligand-dependent transcription factors that control a variety of mammalian physiologies including development, differentiation, proliferation, and homeostasis. Recent studies have found that two nutrient-sensing nuclear receptors, peroxisome proliferator-activated receptor α and farnesoid x receptor, responding to fasting or feeding state, respectively are able to regulate autophagy, an evolutionarily conserved catabolic process involved in lysosomal degradation. In this review, we discuss the role of these nutrient-sensing nuclear receptors in an aspect of transcriptional regulation of autophagy, and how these nuclear receptor-driven transcriptional programs integrate lipophagy, a lipid autophagy with fatty acid oxidation to coordinate hepatic lipid metabolism in the fasted state of the liver...
December 2016: Annals of Pediatric Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28153708/steroidogenic-acute-regulatory-protein-star-overexpression-attenuates-hfd-induced-hepatic-steatosis-and-insulin-resistance
#13
Yanyan Qiu, Xianxian Sui, Yongkun Zhan, Chen Xu, Xiaobo Li, Yanxia Ning, Xiuling Zhi, Lianhua Yin
Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology. Intracellular lipid accumulation is the first step in the development and progression of NAFLD. Steroidogenic acute regulatory protein (StAR) plays an important role in the synthesis of bile acid and intracellular lipid homeostasis and cholesterol metabolism. We hypothesize that StAR is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. The hypothesis was identified using free fatty acid (FFA)-overloaded NAFLD in vitro model and high-fat diet (HFD)-induced NAFLD mouse model transfected by recombinant adenovirus encoding StAR (StAR)...
January 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28146130/effects-of-natural-products-on-fructose-induced-nonalcoholic-fatty-liver-disease-nafld
#14
REVIEW
Qian Chen, Tingting Wang, Jian Li, Sijian Wang, Feng Qiu, Haiyang Yu, Yi Zhang, Tao Wang
As a sugar additive, fructose is widely used in processed foods and beverages. Excessive fructose consumption can cause hepatic steatosis and dyslipidemia, leading to the development of metabolic syndrome. Recent research revealed that fructose-induced nonalcoholic fatty liver disease (NAFLD) is related to several pathological processes, including: (1) augmenting lipogenesis; (2) leading to mitochondrial dysfunction; (3) stimulating the activation of inflammatory pathways; and (4) causing insulin resistance...
January 31, 2017: Nutrients
https://www.readbyqxmd.com/read/28145001/treatment-with-the-natural-fxr-agonist-chenodeoxycholic-acid-reduces-clearance-of-plasma-ldl-whilst-decreasing-circulating-pcsk9-lipoprotein-a-and-apolipoprotein-c-iii
#15
M Ghosh Laskar, M Eriksson, M Rudling, B Angelin
BACKGROUND: The natural farnesoid X receptor (FXR) agonist chenodeoxycholic acid (CDCA) suppresses hepatic cholesterol and bile acid synthesis and reduces biliary cholesterol secretion and triglyceride production. Animal studies have shown that bile acids downregulate hepatic LDL receptors (LDLRs); however, information on LDL metabolism in humans is limited. METHODS: Kinetics of autologous (125) I-LDL were determined in 12 male subjects at baseline and during treatment with CDCA (15 mg kg(-1) day(-1) )...
February 1, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28139275/liver-x-receptor-activation-inhibits-pc-3-prostate-cancer-cells-via-the-beta-catenin-pathway
#16
Kuang Youlin, Zhang Li, He Weiyang, Kang Jian, Liang Siming, Gou Xin
BACKGROUND: Liver X receptors (LXRs) are nuclear receptors family of ligand-dependent transcription factors that play a crucial role in regulating cholesterol metabolism and inflammation. Recent studies show that LXR agonists exhibit anti-cancer activities in a variety of cancer cell lines including prostate. To further identify the potential mechanisms of LXRα activation on prostate cancer, we investigated the effect of LXR agonist T0901317 on PC3 prostate cancer cell and in which activity of beta-catenin pathway involved...
May 12, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28132823/preparation-and-characterisation-of-vandetanib-eluting-radiopaque-beads-for-locoregional-treatment-of-hepatic-malignancies
#17
Alice Hagan, Gary J Phillips, Wendy M Macfarlane, Andrew W Lloyd, Peter Czuczman, Andrew L Lewis
Since their introduction around a decade ago, embolic drug-eluting beads (DEBs) have become a well-established treatment option for the locoregional transarterial treatment of hepatic malignancies. Despite this success, the therapy is seen to be limited by the choice of drug and more effective options are therefore being sought. These include the small molecule multi-tyrosine kinase inhibitors (MTKi), which exert an anti-angiogenic and anti-proliferative effect that could be highly beneficial in combating some of the unwanted downstream consequences of embolization...
January 27, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28130067/farnesoid-x-receptor-activation-promotes-hepatic-amino-acid-catabolism-and-ammonium-clearance-in-mice
#18
Vittoria Massafra, Alexandra Milona, Harmjan R Vos, Rúben J J Ramos, Johan Gerrits, Ellen C L Willemsen, José M Ramos Pittol, Noortje Ijssennagger, Martin Houweling, Hubertus C M T Prinsen, Nanda M Verhoeven-Duif, Boudewijn M Burgering, Saskia W C van Mil
BACKGROUND & AIMS: The nuclear receptor subfamily 1 group H member 4 (NR1H4 or farnesoid X receptor, FXR) regulates bile acid synthesis, transport, and catabolism. FXR also regulates post-prandial lipid and glucose metabolism. We performed quantitative proteomic analyses of liver tissues from mice to evaluate these functions and investigate whether FXR regulates amino acid metabolism. METHODS: To study the role of FXR in mouse liver, we used mice with a disruption of Nr1h4 (FXR-knockout mice) and compared them to floxed control mice...
January 24, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28128444/suppression-of-carboxylesterases-by-imatinib-mediated-by-the-downregulation-of-pregnane-x-receptor
#19
Wenjing Luo, Yu Xin, Xia Zhao, Feng Zhang, Changqing Liu, Hongwei Fan, Tao Xi, Jing Xiong
BACKGROUND AND PURPOSE: Imatinib mesylate (IM) is first-line anti-chronic myeloid leukemia (CML) therapy as a specific inhibitor of BCR-ABL tyrosine kinase. IM in combination with other drugs has been widely applied in CML treatment, thus the influence of IM on drug metabolism enzymes (DMEs) is crucial to be understood in suggesting rational drug administration. Carboxylesterases (CESs) are important enzymes catalyzing hydrolytic biotransformation and play vital roles in the metabolism of numerous clinical drugs...
January 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28128437/schisandrol-b-protects-against-cholestatic-liver-injury-through-pregnane-x-receptor
#20
Hang Zeng, Yiming Jiang, Pan Chen, Xiaomei Fan, Dongshun Li, Aiming Liu, Xiaochao Ma, Wen Xie, Peiqing Liu, Frank J Gonzalez, Min Huang, Huichang Bi
BACKGROUND AND PURPOSE: Currently, ursodeoxycholic acid is the only FDA-approved drug for limited cholestatic liver diseases, and thus the development of new therapeutic approaches is of great importance. This study aimed to evaluate the anti-cholestasis effect of Schisandrol B (SolB), a bioactive compound isolated from Schisandra sphenanthera. EXPERIMENTAL APPROACH: Hepatoprotective effect of SolB against lithocholic acid (LCA)-induced intrahepatic extrahepatic cholestasis was evaluated in mice...
January 27, 2017: British Journal of Pharmacology
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