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Liver X Receptor

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https://www.readbyqxmd.com/read/29466845/duodenal-niemann-pick-c1-like-1-expression-was-negatively-correlated-with-liver-x-receptor-expression-in-nonalcoholic-fatty-liver-disease
#1
Sang Bong Ahn, Dae Won Jun, Kiseok Jang, Byung Hoon Lee, Kye Jung Shin
Background/Aims: Intestinal cholesterol absorption includes intestinal Niemann-Pick C1-like 1 (NPC1L1) and is an important target pathway in nonalcoholic fatty liver disease (NAFLD). We investigated the expression of NPC1L1 and its correlation with liver X receptor (LXR) expression in peripheral mononuclear (PMN) cells in patients with NAFLD. Methods: We evaluated intestinal expression of NPC1L1 in 25 NAFLD patients and 28 healthy controls. We calculated the mRNA expression levels of LXR and farnesoid X receptor (FXR), which are master players of cholesterol metabolism in PMN cells...
February 23, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29456535/liver-x-receptor-agonist-therapy-prevents-diffuse-alveolar-hemorrhage-in-murine-lupus-by-repolarizing-macrophages
#2
Shuhong Han, Haoyang Zhuang, Stepan Shumyak, Jingfan Wu, Chao Xie, Hui Li, Li-Jun Yang, Westley H Reeves
The generation of CD138+ phagocytic macrophages with an alternative (M2) phenotype that clear apoptotic cells from tissues is defective in lupus. Liver X receptor-alpha (LXRα) is an oxysterol-regulated transcription factor that promotes reverse cholesterol transport and alternative (M2) macrophage activation. Conversely, hypoxia-inducible factor 1-α (HIF1α) promotes classical (M1) macrophage activation. The objective of this study was to see if lupus can be treated by enhancing the generation of M2-like macrophages using LXR agonists...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29454584/fat-specific-protein-27-is-a-novel-target-gene-of-liver-x-receptor-%C3%AE
#3
Daisuke Aibara, Kimihiko Matsusue, Soichi Takiguchi, Frank J Gonzalez, Shigeru Yamano
Fat-specific protein 27 (FSP27) is highly expressed in the fatty liver of genetically obese ob/ob mice and promotes hepatic triglyceride (TG) accumulation. The nuclear hormone receptor liver X receptor α (LXRα) also plays a critical role in the control of TG levels in the liver. The present study demonstrated transcriptional regulation of Fsp27a and Fsp27b genes by LXRα. Treatment with the LXR ligand T0901317 markedly increased Fsp27a and Fsp27b mRNAs in wild-type C57BL/6J and ob/ob mouse livers. A reporter assay indicated that two LXR-responsive elements (LXREs) are necessary for LXRα-dependent induction of Fsp27a and Fsp27b promoter activities...
February 15, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29453462/gq-11-a-new-ppar-agonist-improves-obesity-induced-metabolic-alterations-in-ldlr-mice
#4
Jacqueline C Silva, Edson M de Oliveira, Walter M Turato, Gustavo H G Trossini, Vinícius G Maltarollo, Marina G R Pitta, Ivan R Pitta, Beatriz de Las Heras, Lisardo Boscá, Martina Rudnicki, Dulcineia S P Abdalla
BACKGROUND: Obesity and insulin resistance/diabetes are important risk factors for cardiovascular diseases and demand safe and efficacious therapeutics. OBJECTIVE: To assess the effects of a new thiazolidine compound-GQ-11-on obesity and insulin resistance induced by a diabetogenic diet in LDL receptor-deficient (LDLr -/- ) mice. METHODS: Molecular docking simulations of GQ-11, PPARα and PPARγ structures were performed. Male C57BL/6J LDLr -/- mice fed a diabetogenic diet for 24 weeks were treated with vehicle, GQ-11 or pioglitazone or (20 mg/kg/day) for 28 days by oral gavage...
January 30, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29452375/1%C3%AE-hydroxycholecalciferol-improves-the-growth-performance-and-up-regulates-the-mrna-expression-of-vitamin-d-receptor-in-the-small-intestine-and-kidney-of-broiler-chickens
#5
J C Han, J G Wang, G H Chen, J L Zhang, N Zhang, H X Qu, Y Guo, Y F Yan, X J Yang
1α-Hydroxycholecalciferol (1α-OH-D3) is a vitamin D derivative. The objective of this study was to evaluate the effects of 1α-OH-D3 on the growth and the mRNA expression of vitamin D receptor (VDR) in the small intestine and kidney of chickens. A total of 240 males of one-day-old Ross 308 broilers was randomly assigned to 4 treatments with 5 replicates of 12 birds per replicate. Three levels of 1α-OH-D3 (1.25, 2.5, and 5 μg/kg) were added to a basal diet containing 0.50% calcium (Ca), 0.25% non-phytate phosphorus (NPP), and without supplemental cholecalciferol (vitamin D3)...
February 14, 2018: Poultry Science
https://www.readbyqxmd.com/read/29450657/in-silico-identification-of-small-molecules-as-novel-lxr-agonists-for-the-treatment-of-cardiovascular-disease-and-cancer
#6
Xin Wang, Kaimin Lu, Hao Luo, Danfeng Liang, Xin Long, Yuan Yuan, Chuanfang Wu, Jinku Bao
Liver X receptor (LXR), a member of the nuclear receptor superfamily, mainly serves as a reverse cholesterol transporter in lipid metabolism. It has been demonstrated that LXR is a promising target for the treatment of cardiovascular diseases. LXR is also involved in cancer metabolism, glucose homeostasis, immunity, and various physiological processes. The antitumor function of LXR has become of great interest to researchers in recent years. However, while it is believed that activating LXR with small molecules could be a promising approach to cancer treatment, effective drugs that target LXR are yet to be reported...
February 15, 2018: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29449563/cinacalcet-mediated-activation-of-the-camkk%C3%AE-lkb1-ampk-pathway-attenuates-diabetic-nephropathy-in-db-db-mice-by-modulation-of-apoptosis-and-autophagy
#7
Ji Hee Lim, Hyung Wook Kim, Min Young Kim, Tae Woo Kim, Eun Nim Kim, Yaeni Kim, Sungjin Chung, Young Soo Kim, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Hye Won Kim, Cheol Whee Park
Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca2+ concentration and the phosphorylation of Ca2+ /calmodulin-dependent protein kinase kinaseβ (CaMKKβ)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29447944/activation-of-liver-x-receptor-%C3%AE-enhancing-neurogenesis-ameliorates-cognitive-impairment-induced-by-chronic-cerebral-hypoperfusion
#8
Ting Sun, Yu-Jiao Li, Qin-Qin Tian, Qi Wu, Dan Feng, Zhe Xue, Yan-Yan Guo, Le Yang, Kun Zhang, Ming-Gao Zhao, Yu-Mei Wu
Chronic cerebral hypoperfusion (CCH), a leading cause of various cerebrovascular diseases, leads to cognitive dysfunction due to neuron loss and impaired neurogenesis. Liver X receptors (LXRs), including LXRα and LXRβ isoforms, are crucial for cholesterol metabolism, synaptic plasticity as well as neurogenesis. However, it is not clear the potential roles of LXRs in the pathogenesis of cognitive impairment induced by CCH. In this study, we demonstrated that LXRβ expression decreased in hippocampus of CCH mice...
February 12, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29446839/siphonaxanthin-a-carotenoid-from-green-algae-inhibits-lipogenesis-in-hepatocytes-via-the-suppression-of-liver-x-receptor-%C3%AE-activity
#9
Jiawen Zheng, Zhuosi Li, Yuki Manabe, Minji Kim, Tsuyoshi Goto, Teruo Kawada, Tatsuya Sugawara
Nonalcoholic fatty liver disease (NAFLD) has shown an increasing morbidity in recent years. Here, we demonstrated that siphonaxanthin (SPX), a rare marine carotenoid, exhibits a strong inhibitory effect on aggravated hepatic lipogenesis in vitro and would be a promising candidate in the prevention and alleviation of NAFLD in the future. In this study, we conducted a preliminary assessment of the effect of SPX on hepatic lipogenesis by using the HepG2 cell line, derived from human liver cancer, as a model of the liver...
February 15, 2018: Lipids
https://www.readbyqxmd.com/read/29446652/developmental-regulation-of-the-intestinal-fgf19-system-in-domestic-pigs
#10
Aleix Gavaldà-Navarro, Jose J Pastor, Alessandro Mereu, Francesc Villarroya, Ignacio R Ipharraguerre
Fibroblast growth factor-19 (FGF19) is an emerging endocrine factor involved in the regulation of bile acid homeostasis and energy metabolism in rodents and humans. In pigs, however, the FGF19 system remains largely unexplored. This study was designed to investigate the developmental regulation of the FGF19 system in domestic pigs. Samples of intestinal sections, liver, and plasma were collected from 24 pigs (n = 6) at four developmental stages (birth, pre-weaning, post-weaning, and adulthood). In the intestine, expression of the farnesoid X receptor (FXR) and FGF19 showed a congruent time- and region-dependent regulation, beginning soon after birth to achieve maximal expression in ileum during adulthood...
February 15, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29438418/bile-acid-detoxifying-enzymes-limit-susceptibility-to-liver-fibrosis-in-female-shrsp5-dmcr-rats-fed-with-a-high-fat-cholesterol-diet
#11
Husna Yetti, Hisao Naito, Yuan Yuan, Xiaofang Jia, Yumi Hayashi, Hazuki Tamada, Kazuya Kitamori, Katsumi Ikeda, Yukio Yamori, Tamie Nakajima
During middle age, women are less susceptible to nonalcoholic steatohepatitis (NASH) than men. Thus, we investigated the underlying molecular mechanisms behind these sexual differences using an established rat model of NASH. Mature female and male stroke-prone spontaneously hypertensive 5/Dmcr rats were fed control or high-fat-cholesterol (HFC) diets for 2, 8, and 14 weeks. Although HFC-induced hepatic fibrosis was markedly less severe in females than in males, only minor gender differences were observed in expression levels of cytochrome P450 enzymes (CYP)7A1, CYP8B1 CYP27A1, and CYP7B1, and multidrug resistance-associated protein 3, and bile salt export pump, which are involved in fibrosis-related bile acid (BA) kinetics...
2018: PloS One
https://www.readbyqxmd.com/read/29436633/microarray-analysis-for-the-identification-of-specific-proteins-and-functional-modules-involved-in-the-process-of-hepatocellular-carcinoma-originating-from-cirrhotic-liver
#12
Wufeng Fan, Guangming Ye
In order to identify the potential pathogenesis of hepatocellular carcinoma (HCC) developing from cirrhosis, a microarray‑based transcriptome profile was analyzed. The GSE63898 expression profile was downloaded from the Gene Expression Omnibus database, which included data from 228 HCC tissue samples and 168 cirrhotic tissue samples. The Robust Multi‑array Average in the Affy package of R was used for raw data processing and Student's t‑test was used to screen differentially expressed genes (DEGs). An enrichment analysis was then conducted using the Database for Annotation, Visualization and Integrated Discovery online tool, and the protein‑protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape...
February 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29435130/o-linked-n-acetylglucosamine-transferase-enhances-secretory-clusterin-expression-via-liver-x-receptors-and-sterol-response-element-binding-protein-regulation-in-cervical-cancer
#13
Min Jun Kim, Mee Young Choi, Dong Hoon Lee, Gu Seob Roh, Hyun Joon Kim, Sang Soo Kang, Gyeong Jae Cho, Yoon Sook Kim, Wan Sung Choi
O-linked N-acetylglucosamine transferase (OGT) expression is increased in various cancer types, indicating the potential importance of O-GlcNAcylation in tumorigenesis. Secretory clusterin (sCLU) is involved in cancer cell proliferation and drug resistance, and recently, liver X receptors (LXRs) and sterol response element binding protein-1 (SREBP-1) were reported to regulate sCLU transcription. Here, we found that sCLU is significantly increased in cervical cancer cell lines, which have higher expression levels of O-GlcNAc and OGT than keratinocytes...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29431742/transcriptional-regulation-of-macrophage-cholesterol-efflux-and-atherogenesis-by-a-long-noncoding-rna
#14
Tamer Sallam, Marius Jones, Brandon J Thomas, Xiaohui Wu, Thomas Gilliland, Kevin Qian, Ascia Eskin, David Casero, Zhengyi Zhang, Jaspreet Sandhu, David Salisbury, Prashant Rajbhandari, Mete Civelek, Cynthia Hong, Ayaka Ito, Xin Liu, Bence Daniel, Aldons J Lusis, Julian Whitelegge, Laszlo Nagy, Antonio Castrillo, Stephen Smale, Peter Tontonoz
Nuclear receptors regulate gene expression in response to environmental cues, but the molecular events governing the cell type specificity of nuclear receptors remain poorly understood. Here we outline a role for a long noncoding RNA (lncRNA) in modulating the cell type-specific actions of liver X receptors (LXRs), sterol-activated nuclear receptors that regulate the expression of genes involved in cholesterol homeostasis and that have been causally linked to the pathogenesis of atherosclerosis. We identify the lncRNA MeXis as an amplifier of LXR-dependent transcription of the gene Abca1, which is critical for regulation of cholesterol efflux...
February 12, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29431552/porcine-interleukin-6-enhances-the-expression-of-cyp2c33-through-a-constitutive-androstane-receptor-retinoid-x-receptor-mediated-pathway
#15
Lixia Xie, Yucheng He, Xiaoqiao Zhou, Xiaowen Li, Xiue Jin, Xiliang Wang, Deshi Shi
1. Cytochrome P450, which is expressed in humans and other animals, is a superfamily of drug-metabolizing enzymes that plays important roles in the metabolism of endogenous and xenobiotic substrates via oxidation, peroxidation, and reduction. Of endogenous substrates, interleukin (IL)-6 is a crucial cytokine involved in inflammation in the liver. The present study aims to elucidate the mechanisms through which IL-6 modulates cytochrome P450 expression. 2. CYP2C33 expression was found to be increased in HepLi cells and primary porcine hepatocytes treated with IL-6 in a concentration-dependent manner...
February 12, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29429758/the-immunobiology-of-mucosal-associated-invariant-t-cell-mait-function-in-primary-biliary-cholangitis-regulation-by-cholic-acid-induced-interleukin-7
#16
Xiang Jiang, Min Lian, Yanmei Li, Weici Zhang, Qixia Wang, Yiran Wei, Jun Zhang, Weihua Chen, Xiao Xiao, Qi Miao, Zhaolian Bian, Dekai Qiu, Jingyuan Fang, Aftab A Ansari, Patrick S C Leung, Ross L Coppel, Ruqi Tang, M Eric Gershwin, Xiong Ma
Mucosal-associated invariant T (MAIT) cells are novel innate-like T cells constituting a significant proportion of circulating and hepatic T cells. Herein, we extensively examine the phenotypical and functional alterations of MAIT cells and their regulation in a cohort of 56 patients with Primary Biliary Cholangitis (PBC) and 53 healthy controls (HC). Additionally alterations of MAIT cells were assessed before and after UDCA treatment. Finally the localization of MAIT cell in liver was examined using specific tetramer staining and the underlying mechanisms of these alterations in PBC were explored...
February 8, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29428667/silybum-marianum-oil-attenuates-hepatic-steatosis-and-oxidative-stress-in-high-fat-diet-fed-mice
#17
Shu Yun Zhu, Ning Jiang, Jing Yang, Jie Tu, Yue Zhou, Xiang Xiao, Ying Dong
In the present study, the effects of Silybum marianum oil (SMO) on hepatic steatosis and oxidative stress were investigated during the development of nonalcoholic fatty liver disease (NAFLD) in high fat diet (HFD)-fed mice. The results showed that body weight, fat mass, and serum biochemical parameters such as triglyceride, free fatty acid, glucose and insulin were reduced by SMO treatment. Meanwhile, SMO decreased the histological injury of liver and the levels of hepatic triglyceride, cholesterol and free fatty acid in HFD-fed mice...
February 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29428525/synthesis-and-activity-evaluation-of-a-series-of-cholanamides-as-modulators-of-the-liver-x-receptors
#18
Mario D Martínez, Alberto A Ghini, M Virginia Dansey, Adriana S Veleiro, Adali Pecci, Lautaro D Alvarez, Gerardo Burton
The Liver X receptors (LXRs) are members of the nuclear receptor family, that play fundamental roles in cholesterol transport, lipid metabolism and modulation of inflammatory responses. In recent years, the synthetic steroid N,N-dimethyl-3β-hydroxycholenamide (DMHCA) arised as a promising LXR ligand. This compound was able to dissociate certain beneficial LXRs effects from those undesirable ones involved in triglyceride metabolism. Here, we synthetized a series of DMHCA analogues with different modifications in the steroidal nucleus involving the A/B ring fusion, that generate changes in the overall conformation of the steroid...
January 31, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29427579/protective-effects-of-yangonin-from-an-edible-botanical-kava-against-lithocholic-acid-induced-cholestasis-and-hepatotoxicity
#19
Yulong Kong, Xiaoguang Gao, Changyuan Wang, Chenqing Ning, Kexin Liu, Zhihao Liu, Huijun Sun, Xiaodong Ma, Pengyuan Sun, Qiang Meng
Accumulation of toxic bile acids in liver could cause cholestasis and liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of yangonin, a product isolated from an edible botanical Kava against lithocholic acid (LCA)-induced cholestasis, and further to elucidate the involvement of farnesoid X receptor (FXR) in the anticholestatic effect using in vivo and in vitro experiments. The cholestatic liver injury model was established by intraperitoneal injections of LCA in C57BL/6 mice...
February 7, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29427522/glucosensing-capacity-of-rainbow-trout-telencephalon
#20
Cristina Otero-Rodiño, Ana Rocha, Rosa Álvarez-Otero, Rosa M Ceinos, Marcos A López-Patiño, Jesús M Míguez, José Miguel Cerdá-Reverter, José L Soengas
To assess the hypothesis of glucosensing systems present in fish telencephalon, we first demonstrated in rainbow trout by in situ hybridization the presence of glucokinase (GK). Then, we assessed the response of glucosensing markers in rainbow trout telencephalon 6h after ICV treatment with glucose or 2-deoxyglucose (inducing glucoprivation). We evaluated the response of parameters related to the mechanisms dependent on GK, liver X receptor (LXR), mitochondrial activity, sweet taste receptor, and sodium-glucose linked transporter 1 (SGLT-1)...
February 10, 2018: Journal of Neuroendocrinology
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