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https://www.readbyqxmd.com/read/28427397/hvc1-ameliorates-hyperlipidemia-and-inflammation-in-ldlr-mice
#1
Se-Yun Cheon, Kyung-Sook Chung, Kyung-Jin Lee, Ho-Young Choi, In-Hye Ham, Dong-Hoon Jung, Yun-Yeop Cha, Hyo-Jin An
BACKGROUND: HVC1 consists of Coptidis Rhizoma (dried rhizome of Coptischinensis), Scutellariae Radix (root of Scutellariabaicalensis), Rhei Rhizoma (rhizome of Rheum officinale), and Pruni Cortex (cortex of Prunusyedoensis Matsum). Although the components are known to be effective in various conditions such as inflammation, hypertension, and hypercholesterolemia, there are no reports of the molecular mechanism of its hypolipidemic effects. METHODS: We investigated the hypolipidemic effect of HVC1 in low-density lipoprotein receptor-deficient (LDLR(-/-)) mice fed a high-cholesterol diet for 13 weeks...
April 20, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28420650/changes-in-lxr-signaling-influence-early-pregnancy-lipogenesis-and-protect-against-dysregulated-fetoplacental-lipid-homeostasis
#2
Vanya Nikolova, Georgia Papacleovoulou, Elena Bellafante, Luiza Borges Manna, Eugene Jansen, Silvère Baron, Shadi Abu-Hayyeh, Malcolm G Parker, Catherine Williamson
Human pregnancy is associated with enhanced de novo lipogenesis in the early stages followed by hyperlipidemia during advanced gestation. Liver X receptors (LXRs) are oxysterol-activated nuclear receptors which stimulate de novo lipogenesis and also promote the efflux of cholesterol from extrahepatic tissues followed by its transport back to the liver for biliary excretion. Although LXR is recognized as a master regulator of triglyceride and cholesterol homeostasis it is unknown whether it facilitates the gestational adaptations in lipid metabolism...
April 18, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28414139/ligand-dependent-and-independent-regulation-of-human-hepatic-sphingomyelin-phosphodiesterase-acid-like-3a-expression-by-pregnane-x-receptor-and-crosstalk-with-liver-x-receptor
#3
Judith Jeske, Andreas Bitter, Wolfgang E Thasler, Thomas S Weiss, Matthias Schwab, Oliver Burk
Pregnane X receptor (PXR) mainly regulates xenobiotic metabolism and detoxification. Additionally, it exerts pleiotropic effects on liver physiology, which in large parts depend on transrepression of other liver-enriched transcription factors. Based on the hypothesis that lower expression levels of PXR may reduce the extent of this inhibition, an exploratory genome-wide transcriptomic profiling was performed using HepG2 cell clones with different expression levels of PXR. This screen and confirmatory real-time RT-PCR identified sphingomyelin phosphodiesterase acid-like (SMPDL) 3A, a novel nucleotide phosphodiesterase and phosphoramidase, as being up-regulated by PXR-deficiency...
April 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28396714/cinnamon-polyphenol-extract-inhibits-hyperlipidemia-and-inflammation-by-modulation-of-transcription-factors-in-high-fat-diet-fed-rats
#4
Zeynep Tuzcu, Cemal Orhan, Nurhan Sahin, Vijaya Juturu, Kazim Sahin
We evaluated the effects of cinnamon polyphenol extract on hepatic transcription factors expressions including SREBP-1c and LXR-α in rats fed high fat diet (HFD). Twenty-eight Wistar rats were allocated into four groups: (i) normal control: animals fed with normal chow; (ii) cinnamon: animals supplemented with cinnamon polyphenol; (iii) HFD: animals fed a high-fat diet; and (iv) HFD + cinnamon: animals fed a high-fat diet and treated with cinnamon polyphenol. Obesity was linked to hyperglycemia, hyperlipidemia, and oxidative stress as imitated by elevated serum glucose, lipid profile, and serum and liver malondialdehyde (MDA) concentrations...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28394474/proteomic-identification-of-rainbow-trout-blood-plasma-proteins-and-their-relationship-to-seminal-plasma-proteins
#5
Joanna Nynca, G J Arnold, T Fröhlich, A Ciereszko
The characterization of fish blood proteomes is important for comparative studies of seminal and blood proteins as well as for the analysis of fish immune mechanisms and pathways. In this study LC-MS/MS and 2D DIGE were applied to compare rainbow trout seminal (SP) and blood plasma (BP) proteomes. The 54 differentially abundant proteins identified in SP are involved in a variety of signalling pathways, including protein ubiquitination, liver X receptor/retinoid X receptor (LXR/RXR) and farnesoid X receptor (FXR)/RXR activation, cell cycle and acute phase signalling...
April 10, 2017: Proteomics
https://www.readbyqxmd.com/read/28369131/liver-x-receptors-activation-through-to901317-binding-reduces-neuroinflammation-in-parkinson-s-disease
#6
Irene Paterniti, Michela Campolo, Rosalba Siracusa, Marika Cordaro, Rosanna Di Paola, Vittorio Calabrese, Michele Navarra, Salvatore Cuzzocrea, Emanuela Esposito
Parkinson's disease (PD) is a neurodegenerative disease in which degeneration of nigrostriatal neurons and inflammation are key players. The aim of our study was to analyze the function of LXRs in neurodegenerative diseases as PD using in vivo, ex vivo and in vitro models of PD; for this purpose, we observed the effects of the LXR agonist, TO901317, in neuroinflammatory pathway related to PD. We performed an in vivo model of PD using the neurotoxin 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) and our results clearly showed that TO901317 administration reduces all of the inflammatory markers involved in PD such as iNOS and COX2, IκB-α and NF-κB...
2017: PloS One
https://www.readbyqxmd.com/read/28367923/hyperglycemia-suppresses-rankl-induced-osteoclast-differentiation-through-lxr%C3%AE-expression-in-raw264-7-cells
#7
Teruyoshi Tanaka, Yuichiro Takei, Nobuhiro Zaima, Tatsuya Moriyama, Dai Yamanouchi
There have been reports that hyperglycemia suppresses osteoclast (OCL) differentiation, although the underlying mechanism is poorly understood. Here we demonstrated that high glucose suppresses OCL differentiation through activation of liver X receptor (LXR) β, a recently reported glucose-sensing nuclear receptor. The effect of hyperglycemia on osteoclastogenesis was tested in RAW264.7 cells, a murine macrophage cell line. Cells were treated with receptor activator of NF-κB ligand (RANKL) under normoglycemic (5...
2017: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/28361293/activation-of-liver-x-receptor-%C3%AE-protects-amyloid-%C3%AE-1-40-induced-inflammatory-and-senescent-responses-in-human-retinal-pigment-epithelial-cells
#8
Bingling Dai, Chunyan Lei, Ru Lin, Lifei Tao, Yue Bin, Hui Peng, Bo Lei
OBJECTIVE: To investigate whether activation of the liver X receptors (LXRs) inhibits amyloid β1-40 (Aβ1-40) induced inflammatory and senescent responses in human retinal pigment epithelial (RPE) cells. MATERIALS AND METHODS: Confluent cultures of human primary RPE and ARPE-19 cells pretreated with 5 μΜ of TO901317 (TO90), a synthetic agonist of LXR, or vehicle were incubated with 1 μΜ of Aβ1-40 or Aβ40-1. The optimum concentrations of Aβ1-40 and TO90 were determined by cell viability assay...
March 30, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28324010/separating-the-anti-inflammatory-and-diabetogenic-effects-of-glucocorticoids-through-lxr%C3%AE-antagonism
#9
Rucha Patel, Lilia Magomedova, Ricky Tsai, Stéphane Angers, Arturo Orellana, Carolyn L Cummins
Synthetic glucocorticoids (GCs), including dexamethasone (DEX), are powerful anti-inflammatory drugs. Long-term use of GCs, however, can result in metabolic side effects such as hyperglycemia, hepatosteatosis, and insulin resistance. The GC receptor (GR) and liver X receptors (LXRα and LXRβ) regulate overlapping genes involved in gluconeogenesis and inflammation. We have previously shown that Lxrβ-/- mice are resistant to the diabetogenic effects of DEX but still sensitive to its immunosuppressive actions...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28315462/implications-of-cerebrovascular-atp-binding-cassette-transporter-g1-abcg1-and-apolipoprotein-m-in-cholesterol-transport-at-the-blood-brain-barrier
#10
Alexandra Carmen Kober, Anil Paul Chirackal Manavalan, Carmen Tam-Amersdorfer, Andreas Holmér, Ahmed Saeed, Elham Fanaee-Danesh, Martina Zandl, Nicole Maria Albrecher, Ingemar Björkhem, Gerhard M Kostner, Björn Dahlbäck, Ute Panzenboeck
Impaired cholesterol/lipoprotein metabolism is linked to neurodegenerative diseases such as Alzheimer's disease (AD). Cerebral cholesterol homeostasis is maintained by the highly efficient blood-brain barrier (BBB) and flux of the oxysterols 24(S)-hydroxycholesterol and 27-hydroxycholesterol, potent liver-X-receptor (LXR) activators. HDL and their apolipoproteins are crucial for cerebral lipid transfer, and loss of ATP binding cassette transporters (ABC)G1 and G4 results in toxic accumulation of oxysterols in the brain...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28300583/synthesis-of-new-c-25-and-c-26-steroidal-acids-as-potential-ligands-of-the-nuclear-receptors-daf-12-lxr-and-gr
#11
María V Dansey, María C Del Fueyo, Adriana S Veleiro, Pablo H Di Chenna
A new methodology to obtain C-25 and C-26 steroidal acids starting from pregnenolone is described. Construction of the side chain was achieved by applying the Mukaiyama aldol reaction with a non-hydrolytic work-up to isolate the trapped silyl enol ether with higher yields. Using this methodology we synthesized three new steroidal acids as potential ligands of DAF-12, Liver X and Glucocorticoid nuclear receptors and studied their activity in reporter gene assays. Our results show that replacement of the 21-CH3 by a 20-keto group in the side chains of the cholestane scaffold of DAF-12 or Liver X receptors ligands causes the loss of the activity...
March 11, 2017: Steroids
https://www.readbyqxmd.com/read/28296229/phytosterol-mediated-inhibition-of-intestinal-cholesterol-absorption-in-mice-is-independent-of-liver-x-receptor
#12
Lídia Cedó, David Santos, Iziar A Ludwig, Reija Silvennoinen, Annabel García-León, Leena Kaipiainen, José M Carbó, Annabel F Valledor, Helena Gylling, Maria-José Motilva, Petri T Kovanen, Miriam Lee-Rueckert, Francisco Blanco-Vaca, Joan Carles Escolà-Gil
SCOPE: Previous studies have proposed that phytosterols activate liver X receptors (LXR) in the intestine, thereby reducing intestinal cholesterol absorption and promoting fecal cholesterol excretion. METHODS AND RESULTS: In the present study, we examined the effects of dietary phytosterol supplementation on intestinal cholesterol absorption and fecal neutral sterol excretion in LXRαβ-deficient mice, and wild-type mice treated with synthetic high-affinity LXRαβ agonists...
March 15, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28273782/active-liver-x-receptor-signaling-in-phagocytes-in-multiple-sclerosis-lesions
#13
Jo Mailleux, Tim Vanmierlo, Jeroen Fj Bogie, Elien Wouters, Dieter Lütjohann, Jerome Ja Hendriks, Jack van Horssen
OBJECTIVE: We sought to determine the liver X receptor (LXR) ligands present in human macrophages after myelin phagocytosis and whether LXRs are activated in multiple sclerosis (MS) lesions. METHODS: We used real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry to determine expression of LXRs and their response genes in human phagocytes after myelin phagocytosis and in active MS lesions. We used gas chromatographic/mass spectrometric analysis to determine LXR-activating oxysterols and cholesterol precursors present and formed in myelin and myelin-incubated cells, respectively...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28270440/liver-x-receptor-%C3%AE-induces-17%C3%AE-hydroxysteroid-dehydrogenase-13-expression-through-srebp-1c
#14
Wen Su, Jun Peng, Sha Li, Yu-Bing Dai, Chun-Jiong Wang, Hu Xu, Min Gao, Xiong-Zhong Ruan, Jan-Ake Gustafsson, Xiao-Yan Zhang, You-Fei Guan
Liver X receptors, including LXRα and LXRβ, are known to be master regulators of liver lipid metabolism. Activation of LXRα increases hepatic lipid storage in lipid droplets (LDs). 17β-hydroxysteroid dehydrogenase-13 (17β-HSD13), a recently identified liver-specific LD-associated protein, has been reported to be involved in the development of nonalcoholic fatty liver disease. However, little is known about its transcriptional regulation. In the present study, we aimed at determining whether 17β-HSD13 gene transcription is controlled by LXRs...
March 7, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28266648/the-trisaccharide-raffinose-modulates-epidermal-differentiation-through-activation-of-liver-x-receptor
#15
Tae-Young Na, Gyeong-Hwan Kim, Hyeon-Jeong Oh, Min-Ho Lee, Yong-Hyun Han, Ki Taek Kim, Ji-Su Kim, Dae-Duk Kim, Mi-Ock Lee
The epidermal barrier function requires optimal keratinocyte differentiation and epidermal lipid synthesis. Liver X receptor (LXR) α and β, are important transcriptional regulators of the epidermal gene expression. Here, we show that raffinose, a ubiquitously present trisaccharide in plants, activated the transcriptional activity of LXRα/β, which led to the induction of genes required for keratinocyte differentiation such as involucrin and filaggrin, and genes involved in lipid metabolism and transport including SCD1 and ABCA1 in both HaCaT and normal human epidermal keratinocytes...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28259649/role-of-the-liver-x-receptors-in-skin-physiology-putative-pharmacological-targets-in-human-diseases
#16
REVIEW
Zangbéwendé Guy Ouedraogo, Allan Fouache, Amalia Trousson, Silvère Baron, Jean-Marc A Lobaccaro
Liver X receptors (LXRs) are members of the nuclear receptor superfamily that have been shown to regulate various physiological functions such as lipid metabolism and cholesterol homeostasis. Concordant reports have elicited the possibility to target them to cure many human diseases including arteriosclerosis, cancer, arthritis, and diabetes. The high relevance of modulating LXR activities to treat numerous skin diseases, mainly those with exacerbated inflammation processes, contrasts with the lack of approved therapeutic use...
March 1, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28258092/impaired-adipose-expansion-caused-by-liver-x-receptor-activation-is-associated-with-insulin-resistance-in-mice-fed-a-high-fat-diet
#17
Yueting Dong, Zhiye Xu, Ziyi Zhang, Xueyao Yin, Xihua Lin, Hong Li, Fenping Zheng
Liver X receptors (LXR) are deemed as potential drug targets for atherosclerosis, whereas a role in adipose tissue expansion and its relation to insulin sensitivity remains unclear. To assess the metabolic effects of LXR activation by the dual LXRα/β agonist T0901317, C57BL/6 mice fed a high-fat diet (HFD) were treated with T0901317 (30 mg/kg once daily by intraperitoneal injection) for 3 weeks. Differentiated 3T3-L1 adipocytes were used for analysing the effect of T0901317 on glucose uptake. The following results were obtained from this study...
April 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28257661/alisol-b-23-acetate-from-the-rhizomes-of-alisma-orientale-is-a-natural-agonist-of-the-human-pregnane-x-receptor
#18
Yuichiro Kanno, Tomofumi Yatsu, Naoya Yamashita, Shuai Zhao, Wei Li, Miyuki Imai, Manami Kashima, Yoshio Inouye, Kiyomitsu Nemoto, Kazuo Koike
BACKGROUND: Pregnane X receptor (PXR) is a key regulator of the induction of drug metabolizing enzymes. PXR has been studied for its importance in drug-drug or herb-drug interactions, and it is also a molecular target for the treatment of inflammatory and metabolic diseases. PURPOSE: This study aims to determine new natural PXR-ligands from traditional plant medicines. METHODS: The PXR activation activity was measured by a mammalian one hybrid assay of PXR...
March 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28244871/expression-of-srebp-1c-requires-srebp-2-mediated-generation-of-a-sterol-ligand-for-lxr-in-livers-of-mice
#19
Shunxing Rong, Víctor A Cortés, Shirya Rashid, Norma N Anderson, Jeffrey G McDonald, Guosheng Liang, Young-Ah Moon, Robert E Hammer, Jay D Horton
The synthesis of cholesterol and fatty acids (FA) in the liver is independently regulated by SREBP-2 and SREBP-1c, respectively. Here, we genetically deleted Srebf-2 from hepatocytes and confirmed that SREBP-2 regulates all genes involved in cholesterol biosynthesis, the LDL receptor, and PCSK9; a secreted protein that degrades LDL receptors in the liver. Surprisingly, we found that elimination of Srebf-2 in hepatocytes of mice also markedly reduced SREBP-1c and the expression of all genes involved in FA and triglyceride synthesis that are normally regulated by SREBP-1c...
February 28, 2017: ELife
https://www.readbyqxmd.com/read/28244008/liver-x-receptor-genes-variants-modulate-als-phenotype
#20
Kevin Mouzat, Nicolas Molinari, Jovana Kantar, Anne Polge, Philippe Corcia, Philippe Couratier, Pierre Clavelou, Raul Juntas-Morales, Nicolas Pageot, Jean -Marc A Lobaccaro, Cedric Raoul, Serge Lumbroso, William Camu
Amyotrophic lateral sclerosis (ALS) is one of the most severe motor neuron (MN) disorders in adults. Phenotype of ALS patients is highly variable and may be influenced by modulators of energy metabolism. Recent works have implicated the liver X receptors α and β (LXRs), either in the propagation process of ALS or in the maintenance of MN survival. LXRs are nuclear receptors activated by oxysterols, modulating cholesterol levels, a suspected modulator of ALS severity. In a cohort of 438 ALS patients and 330 healthy controls, the influence of LXR genes on ALS risk and phenotype was studied using single nucleotide polymorphisms (SNPs)...
February 27, 2017: Molecular Neurobiology
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