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Liver X Receptor

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https://www.readbyqxmd.com/read/28635645/cembrene-diterpenoids-with-ether-linkages-from-sarcophyton-ehrenbergi-an-anti-proliferation-and-molecular-docking-assessment
#1
Mohamed-Elamir F Hegazy, Abdelsamed I Elshamy, Tarik A Mohamed, Ahmed R Hamed, Mahmoud A A Ibrahim, Shinji Ohta, Paul W Paré
Three new cembrene diterpenoids, sarcoehrenbergilid A-C (1-3), along with four known diterpenoids, sarcophine (4), (+)-7α,8β-dihydroxydeepoxysarcophine (5), sinulolide A (6), and sinulolide B (7), and one steroid, sardisterol (8), were isolated and characterized from a solvent extract of the Red Sea soft coral Sarcophyton ehrenbergi. Chemical structures were elucidated by NMR and MS analyses with absolute stereochemistry determined by X-ray analysis. Since these isolated cembrene diterpenes contained 10 or more carbons in a large flexible ring, conformer stabilities were examined based on density functional theory calculations...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28624275/nuclear-receptor-subfamily-1-group-h-member-2-lxrb-is-the-predominant-liver-x-receptor-subtype-regulating-transcription-of-2-major-lipogenic-genes-in-goat-primary-mammary-epithelial-cells
#2
H B Shi, C H Zhang, Z A Xu, X F Xu, Z B Lv, J Luo, J J Loor
In ruminants, recent research has identified a crucial role for liver X receptors (LXR) in regulating lipid metabolism in mammary cells. However, the differences between LXR subtypes in regulating ruminant lipid metabolism are unknown. We used overexpression and knockdown of LXRA and LXRB in goat primary mammary epithelial cells to distinguish subtype-specific regulation of sterol regulatory element binding protein 1c (SREBP1c) and fatty acid synthase (FASN) mRNA expression and their promoter activity. Incubation with siRNA targeting LXR decreased expression of LXRA and LXRB...
June 14, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28621237/role-of-cxcr4-and-sdf1-as-prognostic-factors-for-survival-and-the-association-with-clinicopathology-in-colorectal-cancer-a-systematic-meta-analysis
#3
Yao-Ping Li, Jing Pang, Sheng Gao, Peng-Yu Bai, Wen-da Wang, Pengzhou Kong, Yongping Cui
C-X-C chemokine receptor type 4 and stromal cell-derived factor-1 were proven to play important roles in several types of cancer and in many biological processes connected with tumor growth, invasion, angiogenesis, and metastasis. However, the clinical significance of C-X-C chemokine receptor type 4 and stromal cell-derived factor-1 expression in colorectal cancer remains inaccurate. The purpose of this systematic meta-analysis is to investigate the role of C-X-C chemokine receptor type 4 and stromal cell-derived factor-1 as prognostic factors for survival and the association between C-X-C chemokine receptor type 4/ stromal cell-derived factor-1 and clinicopathology in colorectal cancer...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28619996/farnesoid-x-receptor-and-liver-x-receptor-ligands-initiate-formation-of-coated-platelets
#4
Amanda J Unsworth, Alexander P Bye, Dionne S Tannetta, Michael J R Desborough, Neline Kriek, Tanya Sage, Harriet E Allan, Marilena Crescente, Parveen Yaqoob, Timothy D Warner, Chris I Jones, Jonathan M Gibbins
OBJECTIVES: The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. This, however, seems contradictory with the platelet hyper-reactivity that is associated with several pathological conditions that are associated with increased circulating levels of molecules that are LXR and FXR ligands, such as hyperlipidemia, type 2 diabetes mellitus, and obesity...
June 15, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28617824/regulation-of-type-1-iodothyronine-deiodinase-by-lxr%C3%AE
#5
Yoriko Sakane, Naotetsu Kanamoto, Ichiro Yamauchi, Tetsuya Tagami, Yusuke Morita, Masako Miura, Masakatsu Sone, Akihiro Yasoda, Takeshi Kimura, Kazuwa Nakao, Nobuya Inagaki
The iodothyronine deiodinases are selenoenzymes that regulate the activity of thyroid hormone via specific inner- or outer-ring deiodination. In humans, type 1 deiodinase (D1) is highly expressed in the liver, but the mechanism by which its gene expression is regulated remains to be elucidated. Liver X receptor α (LXRα), a transcription factor of the nuclear receptor superfamily, is highly expressed in the liver, where it functions as a sensor for excess intracellular oxysterols. LXRα interacts with other nuclear receptors on promoters of genes that contain a binding core sequence for nuclear receptors...
2017: PloS One
https://www.readbyqxmd.com/read/28617705/liver-x-receptor-%C3%AE-is-involved-in-counteracting-mechanical-allodynia-by-inhibiting-neuroinflammation-in-the-spinal-dorsal-horn
#6
Jing Xu, Yi-Wei Feng, Ling Liu, Wei Wang, Xiong-Xiong Zhong, Xu-Hong Wei, Xian-Guo Liu
BACKGROUND: Liver X receptors, including α and β isoforms, are ligand-activated transcription factors. Whether liver X receptor α plays a role in neuropathic pain is unknown. METHODS: A spared nerve injury model was established in adult male rats and mice. Von Frey tests were performed to evaluate the neuropathic pain behavior; Western blot and immunohistochemistry were performed to understand the underlying mechanisms. RESULTS: Intrathecal injection of a specific liver X receptor agonist T0901317 or GW3965 could either prevent the development of mechanical allodynia or alleviate the established mechanical allodynia, both in rats and wild-type mice...
June 15, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28611266/retinoid-x-receptor-%C3%AE-dependent-hbv-minichromosome-remodeling-and-viral-replication
#7
Yan Zhang, Song He, Jin-Jun Guo, Hong Peng, Jia-Hao Fan, Qing-Ling Li
BACKGROUND AND AIM: The HBV covalently closed circular DNA (cccDNA) is organized into a minichromosome in the nuclei of infected hepatocytes through interactions with histone and nonhistone proteins. Retinoid X receptor α (RXRα), a liver-enriched nuclear receptor, participates in regulation of HBV replication and transcription through modulation of HBV enhancer 1 and core promoter activity. MATERIAL AND METHODS: This study investigated RXRα involvement in HBV cccDNA epigenetic modifications...
August 1, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28603781/genome-wide-association-studies-candidate-gene-to-dual-modifier-of-nonalcoholic-steatohepatitis-and-atherosclerosis
#8
Clint L Miller, Nicholas J Leeper
Non-alcoholic steatohepatitis (NASH) is a common disease involving chronic accumulation of fat and inflammation in the liver, often leading to advanced fibrosis, cirrhosis and cancer. It is known that NASH shares many features with atherosclerosis, however, there are still no effective therapeutics. In a recent study published in Nature, investigators demonstrate that mice lacking a high-density lipoprotein (HDL)-associated gene were surprisingly protected from both steatohepatitis and atherosclerosis through the stabilization of the liver X receptor (LXR)...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28601022/nrf2-induces-lipocyte-phenotype-via-a-socs3-dependent-negative-feedback-loop-on-jak2-stat3-signaling-in-hepatic-stellate-cells
#9
Chunfeng Lu, Wenxuan Xu, Jiangjuan Shao, Feng Zhang, Anping Chen, Shizhong Zheng
Hepatic stellate cells (HSCs) are universally acknowledged to play a core role in the pathogenesis of hepatic fibrosis. HSCs when activated are characterized by dramatic loss of intracellular lipid droplets. Accumulative evidence has suggested that recovery of lipid droplets could suppress HSC activation. However, the underlying molecular mechanisms still remain largely unclear. In this study, we found that the expression and activity of nuclear factor (erythroid-derived 2) - like 2 (Nrf2) were decreased in activated HSCs and negatively correlated with hepatic fibrosis severity in human liver specimens...
June 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28591793/dynamics-of-bile-acid-profiles-glp-1-and-fgf19-after-laparoscopic-gastric-banding
#10
Veronika Thöni, Alexandra Pfister, Andreas Melmer, Barbara Enrich, Karin Salzmann, Susanne Kaser, Claudia Lamina, Christoph F Ebenbichler, Hubert Hackl, Herbert Tilg, Alexander R Moschen
Context: Increase of bile acids (BAs), fibroblast growth factor 19 (FGF19) and glucagon-like peptide 1 (GLP-1) has been implicated in metabolic improvements after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), whereas data are still conflicting regarding their role after laparoscopic adjustable gastric banding (LAGB). Objective: To assess fasting BA, FGF19 and GLP-1 concentrations in plasma before and after LAGB and to test for correlations with immuno-metabolic parameters...
June 7, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28588695/canonical-and-alternative-transcript-expression-of-pax6-and-cxcr4-in-pancreatic-cancer
#11
Elizabeth C Little, Jennifer D Kubic, Ravi Salgia, Paul J Grippo, Deborah Lang
Pancreatic cancer is a lethal disease with a propensity for invading and metastasizing into the surrounding tissues, including the liver and intestines. A number of factors are aberrantly overexpressed in this tumor type and actively promote cancer progression and metastasis. The present study demonstrates that paired box transcription factor 6 (PAX6) and C-X-C chemokine receptor 4 (CXCR4) are frequently co-expressed in primary pancreatic adenocarcinoma tumors and established cell lines. Expression analysis methods used in the present study included evaluation of protein expression by western blot analysis and immunofluorescence, transcript expression levels by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and luciferase assays utilizing regulatory elements from the CXCR4 gene locus...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28586124/shp-deletion-prevents-hepatic-steatosis-and-when-combined-with-fxr-loss-protects-against-type-2-diabetes
#12
Oludemilade Akinrotimi, Ryan Riessen, Philip VanDuyne, Jung Eun Park, Yoon Kwang Lee, Lee-Jun Wong, Ann M Zavacki, Kristina Schoonjans, Sayeepriyadarshini Anakk
Nuclear receptors Farnesoid X Receptor (FXR) and Small Heterodimer Partner (SHP) are important regulators of bile acid, lipid and glucose homeostasis. Here we show that global Fxr (-/-) Shp(-/-) double knockout (DKO) mice are refractory to weight gain, glucose intolerance and hepatic steatosis when challenged with high-fat diet. DKO mice display an inherently increased capacity to burn fat and suppress de novo hepatic lipid synthesis. Moreover, DKO mice are also very active and that correlates well with the observed increase in Pepck expression, type IA fibers and mitochondrial function in the skeletal muscle...
June 6, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28583767/lxr-dependent-regulation-of-macrophage-specific-reverse-cholesterol-transport-is-impaired-in-a-model-of-genetic-diabesity
#13
Teresa L Errico, Karen Alejandra Méndez-Lara, David Santos, Núria Cabrerizo, Lucía Baila-Rueda, Jari Metso, Ana Cenarro, Eva Pardina, Albert Lecube, Matti Jauhiainen, Julia Peinado-Onsurbe, Joan Carles Escolà-Gil, Francisco Blanco-Vaca, Josep Julve
Diabesity and fatty liver have been associated with low levels of high-density lipoprotein cholesterol, and thus could impair macrophage-specific reverse cholesterol transport (m-RCT). Liver X receptor (LXR) plays a critical role in m-RCT. Abcg5/g8 sterol transporters, which are involved in cholesterol trafficking into bile, as well as other LXR targets, could be compromised in the livers of obese individuals. We aimed to determine m-RCT dynamics in a mouse model of diabesity, the db/db mice. These obese mice displayed a significant retention of macrophage-derived cholesterol in the liver and reduced fecal cholesterol elimination compared with nonobese mice...
May 18, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28583434/27-hydroxycholesterol-a-novel-player-in-molecular-carcinogenesis-of-breast-and-prostate-cancer
#14
REVIEW
Gurdeep Marwarha, Shaneabbas Raza, Kimberly Hammer, Othman Ghribi
Several studies have suggested an etiological role for hypercholesterolemia in the pathogenesis of breast cancer and prostate cancer (PCa). However, the molecular mechanisms that underlie and mediate the hypercholesterolemia-fostered increased risk for breast cancer and PCa are yet to be determined. The discovery that the most abundant cholesterol oxidized metabolite in the plasma, 27 hydroxycholesterol (27-OHC), is a selective estrogen receptor modulator (SERM) and an agonist of Liver X receptors (LXR) partially fills the void in our understanding and knowledge of the mechanisms that may link hypercholesterolemia to development and progression of breast cancer and PCa...
June 2, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28580131/recent-insights-into-the-implications-of-metabolism-in-plasmacytoid-dendritic-cell-innate-functions-potential-ways-to-control-these-functions
#15
REVIEW
Philippe Saas, Alexis Varin, Sylvain Perruche, Adam Ceroi
There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β)...
2017: F1000Research
https://www.readbyqxmd.com/read/28579886/d-4f-decreases-the-expression-of-a%C3%AE-protein-through-up-regulating-long-non-coding-rna-sirt1-as-in-samp8-mice
#16
Xiao-Han Ding, Jie Han, Yuan Liu, Ying Jin, Ping Ye
Cholesterol plays key roles on (Aβ) metabolism and production. D-4F is the apolipoprotein A-I mimetic peptide which has been revealed a critical role in regulation cholesterol. We aimed at identifying the effects of D-4F on Aβ production in SAMP8 and the underlying mechanisms. METHODS: SAMP8 mice (n = 15) were randomized into three groups for treatment with D-4F given in drinking water: high-dose group (0.5 mg/ml), low-dose group (0.3 mg/ml) and control group (just drinking water)...
May 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28576574/physical-and-functional-interactions-between-nuclear-receptor-lxr%C3%AE-and-the-forkhead-box-transcription-factor-foxa2-regulate-the-response-of-the-human-lipoprotein-lipase-gene-to-oxysterols-in-hepatic-cells
#17
Maria Kanaki, Ioanna Tiniakou, Efstathia Thymiakou, Dimitris Kardassis
Lipoprotein lipase (LPL) catalyzes the hydrolysis of triglycerides from triglyceride-rich lipoproteins such as VLDL and chylomicrons in the circulation. Mutations in LPL or its activator apolipoprotein C-II cause hypertriglyceridemia in humans and animal models. The levels of LPL in the liver are low but they can be strongly induced by a high cholesterol diet or by synthetic ligands of Liver X Receptors (LXRs). However, the mechanism by which LXRs activate the human LPL gene is unknown. In the present study we show that LXR agonists increased the mRNA and protein levels as well as the promoter activity of human LPL in HepG2 cells...
May 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28576406/puerarin-promotes-abca1-mediated-cholesterol-efflux-and-decreases-cellular-lipid-accumulation-in-thp-1-macrophages
#18
Cong-Hui Li, Duo Gong, Ling-Yan Chen, Min Zhang, Xiao-Dan Xia, Hai-Peng Cheng, Chong Huang, Zhen-Wang Zhao, Xi-Long Zheng, Xiao-Er Tang, Chao-Ke Tang
It was reported that puerarin decreases the total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and increases high-density lipoprotein cholesterol (HDL-C) level, but the underlying mechanism is unclear. This study was designed to determine whether puerarin decreased lipid accumulation via up-regulation of ABCA1-mediated cholesterol efflux in THP-1 macrophage-derived foam cells. Our results showed that puerarin significantly promoted the expression of ATP-binding cassette transporter A1 (ABCA1) mRNA and protein via the AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma (PPARγ)-liver X receptor-alpha (LXR-α) pathway and decreased cellular lipid accumulation in human THP-1 macrophage-derived foam cells...
May 30, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28571685/activation-of-the-aryl-hydrocarbon-receptor-decreases-rifampicin-induced-cyp3a4-expression-in-primary-human-hepatocytes-and-heparg
#19
Martin Krøyer Rasmussen, Martine Daujat-Chavanieu, Sabine Gerbal-Chaloin
The role of the cross-talk between nuclear receptors in the regulation of Cytochrome P450 expression in the liver is well-documented. Most studies have focused on the cross-talk between the pregnane X receptor (PXR) and other receptors, such as the constitutive androstane receptor. However, cross-talk between PXRs and aryl hydrocarbon receptors (AhRs) has also been suggested, but reports regarding this cross-talk are conflicting. In the present study, we treated HepaRG and primary human hepatocytes (PHHs) with both a strong (TCDD) and weak (3-methylindole; 3MI) AhR activator to investigate their impact on PXR-regulated expression of CYP3A4...
May 29, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28560400/altered-gene-expression-of-hepatic-cytochrome-p450-in-a-rat-model-of-intermittent-hypoxia-with-emphysema
#20
Hongzhi Yu, Hongxia Shao, Qi Wu, Xin Sun, Li Li, Kuan Li, Xue Li, Yu Li, Qiuyang Zhang, Junping Wu, Huaiyong Chen
Patients with respiratory overlap syndrome (OS), defined as concomitant chronic obstructive pulmonary disease and obstructive sleep apnea syndrome, may exhibit an increased blood concentration of ingested drugs. This poor elimination of drugs is primarily attributed to downregulated gene expression of the drug‑metabolizing cytochrome P450 enzymes (CYPs) in the liver. However, the underlying mechanisms of the decreased expression of CYPs in OS are poorly understood. In order to address this, a rat model of intermittent hypoxia with emphysema was evaluated in the present study, by analyzing liver gene expression using the reverse transcription‑quantitative polymerase chain reaction...
July 2017: Molecular Medicine Reports
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