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Liver X Receptor

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https://www.readbyqxmd.com/read/27922847/apolipoprotein-e-metabolism-and-functions-in-brain-and-its-role-in-alzheimer-s-disease
#1
Fan Liao, Hyejin Yoon, Jungsu Kim
PURPOSE OF REVIEW: APOE4 genotype is the strongest genetic risk factor for Alzheimer's disease. Prevailing evidence suggests that amyloid β plays a critical role in Alzheimer's disease. The objective of this article is to review the recent findings about the metabolism of apolipoprotein E (ApoE) and amyloid β and other possible mechanisms by which ApoE contributes to the pathogenesis of Alzheimer's disease. RECENT FINDINGS: ApoE isoforms have differential effects on amyloid β metabolism...
December 5, 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27918553/jagged-1-is-a-major-notch-ligand-along-cholangiocarcinoma-development-in-mice-and-humans
#2
L Che, B Fan, M G Pilo, Z Xu, Y Liu, A Cigliano, A Cossu, G Palmieri, R M Pascale, A Porcu, G Vidili, M Serra, F Dombrowski, S Ribback, D F Calvisi, X Chen
Intrahepatic cholangiocarcinoma (ICC) is a rare yet deadly malignancy with limited treatment options. Activation of the Notch signalling cascade has been implicated in cholangiocarcinogenesis. However, while several studies focused on the Notch receptors required for ICC development, little is known about the upstream inducers responsible for their activation. Here, we show that the Jagged 1 (Jag1) ligand is almost ubiquitously upregulated in human ICC samples when compared with corresponding non-tumorous counterparts...
December 5, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27916310/effects-of-chronic-dietary-exposure-of-zinc-oxide-nanoparticles-on-the-serum-protein-profile-of-juvenile-common-carp-cyprinus-carpio-l
#3
Latifeh Chupani, Eliška Zusková, Hamid Niksirat, Aleš Panáček, Vanessa Lünsmann, Sven-Bastiaan Haange, Martin von Bergen, Nico Jehmlich
Zinc oxide (ZnO) nanoparticles (NPs) have been dramatically used in industry, biology, and medicine. Despite their interesting physico-chemical properties for application in various industrial, medical, and consumer products, safe use of ZnO NPs are under challenges due to the inadequate information related to their toxicological endpoints. Proteomics was applied to evaluate the sub-lethal effects of dietary exposure to ZnO NPs on serum proteome profile of juvenile common carp, (Cyprinus carpio). Therefore, ZnO NPs solution (500mgkg(-1) of feed) was added to a commercial carp feed for six weeks...
December 1, 2016: Science of the Total Environment
https://www.readbyqxmd.com/read/27914812/protective-effects-of-gomisin-n-against-hepatic-steatosis-through-ampk-activation
#4
Ye-Rang Yun, Ji-Hyun Kim, Ji Ha Kim, Myeong Ho Jung
Gomisin N (GN) is a phytochemical derived from Schisandra chinensis. It has been reported to exert a protective effect against hepatic steatosis by attenuating endoplasmic recticulum (ER) stress. However, the detailed mechanism by which GN inhibits hepatic steatosis remains to be elucidated. In this study, we examined whether GN activates AMP-activated protein kinase (AMPK) and exerts therapeutic effects on liver X receptor (LXR)- or palmitic acid (PA)-induced triglyceride (TG) accumulation in HepG2 cells. Furthermore, in vivo protective effects of GN against hepatic steatosis were assessed in high-fat diet (HFD)-induced obese mice...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27914036/prolactin-regulatory-element-binding-protein-is-involved-in-suppression-of-the-adiponectin-gene-in-vivo
#5
X Z Zhang, H Imachi, J Y Lyu, K Fukunaga, S Sato, T Ibata, T Kobayashi, T Yoshimoto, F Kikuchi, T Dong, K Murao
PURPOSE: Prolactin regulatory element-binding protein (PREB), a member of the WD-repeat protein family, has been recognized as a transcriptional factor that regulates prolactin promoter activity in the anterior pituitary of rats. PREB is expressed not only in the pituitary but also in various other tissues, including the adipose tissue. Previous studies have shown that PREB acts as a transcriptional regulator and suppresses the expression of the adiponectin gene in cultured 3T3L1 preadipocytes...
December 2, 2016: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/27913621/identification-of-hepatic-lysophosphatidylcholine-acyltransferase-3-as-a-novel-target-gene-regulated-by-peroxisome-proliferator-activated-receptor-%C3%AE
#6
Amar Bahadur Singh, Jingwen Liu
Peroxisome proliferator-activated receptor δ (PPARδ) regulates many genes involved in lipid metabolism. Hepatic lysophosphatidylcholine acyltransferase 3 (LPCAT3) has critical functions in triglycerides transport and ER stress response due to its unique ability to catalyze the incorporation of polyunsaturated fatty acids into phospholipids. Previous studies identified liver X receptor as the transcription factor controlling LPCAT3 expression in mouse liver tissue. Here we show that the hepatic LPCAT3 gene is transcriptionally regulated by PPARδ...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909409/3-5-3-triiodo-l-thyronine-and-3-5-diiodo-l-thyronine-affected-metabolic-pathways-in-liver-of-ldl-receptor-deficient-mice
#7
Maria Moreno, Elena Silvestri, Maria Coppola, Ira J Goldberg, Li-Shin Huang, Anna M Salzano, Fulvio D'Angelo, Joel R Ehrenkranz, Fernando Goglia
3,5,3'-triiodo-L-thyronine (T3) and 3,5-diiodo-L-thyronine (T2), when administered to a model of familial hypercholesterolemia, i.e., low density lipoprotein receptor (LDLr)-knockout (Ldlr(-/-)) mice fed with a Western type diet (WTD), dramatically reduce circulating total and very low-density lipoprotein/LDL cholesterol with decreased liver apolipoprotein B (ApoB) production. The aim of the study was to highlight putative molecular mechanisms to manage cholesterol levels in the absence of LDLr. A comprehensive comparative profiling of changes in expression of soluble proteins in livers from Ldlr(-/-) mice treated with either T3 or T2 was performed...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27903618/hypolipidemic-effect-of-oleanolic-acid-is-mediated-by-the-mir-98-5p-pgc-1%C3%AE-axis-in-high-fat-diet-induced-hyperlipidemic-mice
#8
Siyu Chen, Xiaoan Wen, Wenxiang Zhang, Chen Wang, Jun Liu, Chang Liu
Oleanolic acid (OA) is an active component of the traditional Chinese herb olea europaea l. and has been found to exhibit a significant lipid-lowering effect; however, its direct molecular target is still unknown, which limits its clinical application and the possible structure modification to improve its beneficial functions. In this regard, we carried out the present study to identify potential hepatic targets of OA to mediate its lipid-lowering effect. We found that both acute and chronic OA treatments reduced serum levels of triglycerides, total cholesterol, and LDL cholesterol, and decreased hepatic expression levels of peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β), which is an important regulator in maintaining hepatic lipid homeostasis, and its downstream target genes...
November 30, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27899892/age-dependent-hepatic-udp-glucuronosyltransferase-gene-expression-and-activity-in-children
#9
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/27898934/an-insufficient-glucose-supply-causes-reduced-lactose-synthesis-in-lactating-dairy-cows-fed-rice-straw-instead-of-alfalfa-hay
#10
B Wang, F-Q Zhao, B-X Zhang, J-X Liu
The objective of the present study was to investigate the nutrient availability for milk production in the mammary gland of lactating cows fed different forage-based diets. The 3 diets contained 30% corn stover (CS), 30% rice straw (RS), or 23% alfalfa hay plus 7% Chinese wild rye hay (AH) as a forage source. All diets contained 15% of DM as corn silage and 55% of DM as concentrate. The percentage of milk lactose was always lower in the RS-fed cows than in the cows fed AH or CS during the 12-wk feeding trial ( < 0...
November 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27896916/dihydroartemisinin-counteracts-fibrotic-portal-hypertension-via-farnesoid-x-receptor-dependent-inhibition-of-hepatic-stellate-cell-contraction
#11
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/27895393/emerging-role-of-obeticholic-acid-in-the-management-of-nonalcoholic-fatty-liver-disease
#12
EDITORIAL
Evangelia Makri, Evangelos Cholongitas, Konstantinos Tziomalos
Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is associated with increased risk for cardiovascular disease and hepatocellular cancer. Diet and exercise are limited by suboptimal long-term adherence in patients with NAFLD. On the other hand, current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In this context, obeticholic acid (OCA), a selective agonist of the farnesoid X receptors, might represent a useful option in these patients...
November 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27889186/circadian-homeostasis-of-liver-metabolism-suppresses-hepatocarcinogenesis
#13
Nicole M Kettner, Horatio Voicu, Milton J Finegold, Cristian Coarfa, Arun Sreekumar, Nagireddy Putluri, Chinenye A Katchy, Choogon Lee, David D Moore, Loning Fu
Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a mechanism very similar to that observed in obese humans. The process initiates with non-alcoholic fatty liver disease (NAFLD) that progresses to steatohepatitis and fibrosis before HCC detection. This pathophysiological pathway is driven by jet-lag-induced genome-wide gene deregulation and global liver metabolic dysfunction, with nuclear receptor-controlled cholesterol/bile acid and xenobiotic metabolism among the top deregulated pathways...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27888103/luteolin-improves-non-alcoholic-fatty-liver-disease-in-db-db-mice-by-inhibition-of-liver-x-receptor-activation-to-down-regulate-expression-of-sterol-regulatory-element-binding-protein-1c
#14
Ye Yin, Lu Gao, Haiyan Lin, Yue Wu, Xiao Han, Yunxia Zhu, Jie Li
In this study, we report that daily administration of luteolin for 8 weeks improved hepatic steatosis by repressing hepatic TG accumulation and increasing glycogen storage. Luteolin inhibited hepatic de novo lipid synthesis by regulating the LXR-SREBP-1c signaling pathway, which is over-activated in the livers of db/db mice. Further in vitro studies revealed that luteolin can competitively bind to the ligand binding domain to suppress the LXR activation induced by an LXR agonist and high glucose, thereby decreasing TG accumulation in HepG2 cells and primary hepatocytes...
November 22, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27870652/fatty-acid-metabolism-in-macrophages-a-target-in-cardio-metabolic-diseases
#15
Louise Ménégaut, Charles Thomas, Laurent Lagrost, David Masson
PURPOSE OF REVIEW: Recent studies have highlighted that macrophages dynamically and autonomously handle all the facets of fatty acid (FA) metabolism including FA oxidation and FA synthesis as well as the synthesis of monounsaturated FAs and long chain n-3 and n-6 polyunsaturated FAs. RECENT FINDINGS: Macrophage M2 polarization is associated with an increase of FA oxidation. However, whether increased FA oxidation simply correlates with or is required for M2 polarization needs to be further evaluated...
November 18, 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27869139/the-transcription-cofactor-crtc1-protects-from-aberrant-hepatic-lipid-accumulation
#16
Hwijin Kim
Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging global health-problem. NAFLD encompasses a range of conditions associated with hepatic steatosis, aberrant accumulation of fat in hepatocytes. Although obesity and metabolic syndrome are considered to have a strong association with NAFLD, genetic factors that predispose liver to NAFLD and molecular mechanisms by which excess hepatic lipid develops remain largely unknown. We report that the transcription cofactor CRTC1 confers broad spectrum protection against hepatic steatosis development...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27865854/obeticholic-acid-protects-against-carbon-tetrachloride-induced-acute-liver-injury-and-inflammation
#17
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/27856527/role-of-glucocorticoid-receptor-and-pregnane-x-receptor-in-dexamethasone-induction-of-rat-hepatic-aryl-hydrocarbon-receptor-nuclear-translocator-and-nadph-cytochrome-p450-oxidoreductase
#18
Sarah R Hunter, Alex Vonk, Anne K Mullen Grey, David S Riddick
The aryl hydrocarbon receptor (AHR) nuclear translocator (ARNT), as the AHR's heterodimerization partner, and NADPH-cytochrome P450 oxidoreductase (POR), as the key electron donor for all microsomal P450s, are independent and indispensable components in the adaptive and toxic responses to polycyclic aromatic hydrocarbons. Expression of both ARNT and POR in rat liver is induced by dexamethasone (DEX), a synthetic glucocorticoid known to activate both the glucocorticoid receptor (GR) and the pregnane X receptor (PXR)...
November 16, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27853109/a-crucial-role-of-constitutive-androstane-receptor-car-in-liver-tumor-development-by-imazalil-in-mice
#19
Kei Tamura, Kaoru Inoue, Miwa Takahashi, Saori Matsuo, Yukio Kodama, Midori Yoshida
To clarify the major pathway of liver tumor development induced by imazalil (IMA), an imidazole fungicide, male constitutive androstane receptor (CAR)-knockout (CARKO) and wild-type (WT) mice were treated with IMA at 500 ppm in the diet up to 27 weeks after initiation by diethylnitrosamine. After 27 weeks of treatment, neither altered foci nor adenomas were significantly increased in CARKO mice, whereas both eosinophilic altered foci and adenomas were increased in WT mice. After 4 or 13 weeks of IMA treatment, liver hypertrophy was observed at the tumor-inducible dose without differences among genotypes or durations...
2016: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/27852305/schisandra-polysaccharide-inhibits-hepatic-lipid-accumulation-by-downregulating-expression-of-srebps-in-nafld-mice
#20
Chun-Mei Wang, Rong-Shuang Yuan, Wen-Yue Zhuang, Jing-Hui Sun, Jin-Ying Wu, He Li, Jian-Guang Chen
BACKGROUND: Hepatoprotective effects of Chinese herbal medicine Schisandra Chinensis (Schisandra) have been widely investigated. However, most studies were focused on its lignan extracts. We investigated the effects of Schisandra polysaccharide (SCP) in a mouse model of non-alcoholic fatty liver disease (NAFLD), and studied its effect on sterol regulatory element binding proteins (SREBPs) and the related genes. METHODS: The mouse model of NAFLD was established by feeding mice with a high-fat diet for 16 weeks...
November 16, 2016: Lipids in Health and Disease
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