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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
#1
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/28619996/farnesoid-x-receptor-and-liver-x-receptor-ligands-initiate-formation-of-coated-platelets
#2
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
#3
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/28603781/genome-wide-association-studies-candidate-gene-to-dual-modifier-of-nonalcoholic-steatohepatitis-and-atherosclerosis
#4
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/28583767/lxr-dependent-regulation-of-macrophage-specific-reverse-cholesterol-transport-is-impaired-in-a-model-of-genetic-diabesity
#5
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
#6
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/28583294/hataedock-treatment-has-preventive-therapeutic-effects-for-atopic-dermatitis-through-skin-barrier-protection-in-dermatophagoides-farinae-induced-nc-nga-mice
#7
Ho-Yeol Cha, Sang-Hyun Ahn, Jin-Hong Cheon, Sun-Young Park, Kibong Kim
ETHNOPHARMACOLOGICAL RELEVANCE: Hataedock treatment is traditionally used for the purpose of preventing the future skin disease by feeding herbal extracts to the newborn in traditional Chinese and Korean medicine. AIM OF THE STUDY: This study investigated the preventive therapeutic effects of Hataedock (HTD) treatment for atopic dermatitis (AD) through skin barrier protection in Dermatophagoides farinae-induced NC/Nga mice. MATERIALS AND METHODS: To the HTD treatment group, the extract of Coptis japonica Makino and Glycyrrhiza uralensis Fischer, which analyzed with High Performance Liquid Chromatography (HPLC)-fingerprint for quality consistency, was administered orally to the 3-week-old mice before inducing AD...
June 3, 2017: Journal of Ethnopharmacology
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
#8
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/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
#9
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
#10
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/28573829/comparative-proteomic-profiling-of-the-serum-differentiates-pancreatic-cancer-from-chronic-pancreatitis
#11
Mayank Saraswat, Sakari Joenväärä, Hanna Seppänen, Harri Mustonen, Caj Haglund, Risto Renkonen
Finland ranks sixth among the countries having highest incidence rate of pancreatic cancer with mortality roughly equaling incidence. The average age of diagnosis for pancreatic cancer is 69 years in Nordic males, whereas the average age of diagnosis of chronic pancreatitis is 40-50 years, however, many cases overlap in age. By radiology, the evaluation of a pancreatic mass, that is, the differential diagnosis between chronic pancreatitis and pancreatic cancer is often difficult. Preoperative needle biopsies are difficult to obtain and are demanding to interpret...
June 1, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28560318/differential-effects-of-retinoic-acid-concentrations-in-regulating-blood-brain-barrier-properties
#12
Stephanie Bonney, Julie A Siegenthaler
The blood-brain barrier (BBB) is a multifaceted property of the brain vasculature that protects the brain and maintains homeostasis by tightly regulating the flux of ions, molecules, and cells across the vasculature. Blood vessels in the brain are formed by endothelial cells that acquire barrier properties, such as tight and adherens junctions, soon after the brain vasculature is formed. Endothelial WNT signaling is crucial to induce these BBB properties by regulating their expression and stabilization. Recent studies have implicated retinoic acid (RA) signaling in BBB development and shown that pharmacological concentrations of RA (≥5 µm) can induce BBB properties in cultured brain endothelial cells...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28555747/liver-x-receptors-link-lipid-metabolism-and-inflammation
#13
REVIEW
Ira G Schulman
The response of immune cells to pathogens is often associated with changes in the flux through basic metabolic pathways. Indeed, in many cases changes in metabolism appear to be necessary for a robust immune response. The Liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily that regulate gene networks controlling cholesterol and lipid metabolism. In immune cells, particularly in macrophages, LXRs also inhibit pro-inflammatory gene expression. This Review will highlight recent studies that connect LXR-dependent control of lipid metabolism to regulation of the immune response...
May 27, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28552552/b-13-progenitor-derived-hepatocytes-b-13-h-cells-model-lipid-dysregulation-in-response-to-drugs-and-chemicals
#14
Alistair C Leitch, Philip M E Probert, James A Shayman, Stephanie K Meyer, George E N Kass, Matthew C Wright
Lipid dysregulation is a common hepatic adverse outcome after exposure to toxic drugs and chemicals. A donor-free rat hepatocyte-like (B-13/H) cell was therefore examined as an in vitro model for investigating mechanisms. The B-13/H cell irreversibly accumulated triglycerides (steatosis) in a time- and dose-dependent manner when exposed to fatty acids, an effect that was potentiated by the combined addition of hyperglycaemic levels of glucose and insulin. B-13/H cells also expressed the LXR nuclear receptors and exposure to their activators - T0901317 or GW3965 - induced luciferase expression from a transfected LXR-regulated reporter gene construct and steatosis in a dose-dependent manner with T0901317...
May 25, 2017: Toxicology
https://www.readbyqxmd.com/read/28549691/27-hydroxycholesterol-upregulates-the-production-of-heat-shock-protein-60-of-monocytic-cells
#15
Bo-Young Kim, Yonghae Son, Jeongyoon Choi, Seong-Kug Eo, Young Chul Park, Koanhoi Kim
Investigating differentially expressed proteins in a milieu rich in cholesterol oxidation products, we found via mass spectrometry-based proteomics that surface levels of heat shock protein 60 (HSP60) were upregulated on monocytic cells in the presence of 27-hydroxycholesterol (27OHChol). The elevated levels of cytoplasmic membrane HSP60 were verified via Western blot analysis and visualized by confocal microscopy. Treatment with 27OHChol also resulted in increased levels of cellular HSP60 without altering its transcription...
May 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28546081/targeting-nuclear-receptors-for-the-treatment-of-fatty-liver-disease
#16
REVIEW
Naoki Tanaka, Toshifumi Aoyama, Shioko Kimura, Frank J Gonzalez
Ligand-activated nuclear receptors, including peroxisome proliferator-activated receptor alpha (PPARα), pregnane X receptor, and constitutive androstane receptor, were first identified as key regulators of the responses against chemical toxicants. However, numerous studies using mouse disease models and human samples have revealed critical roles for these receptors and others, such as PPARβ/δ, PPARγ, farnesoid X receptor (FXR), and liver X receptor (LXR), in maintaining nutrient/energy homeostasis in part through modulation of the gut-liver-adipose axis...
May 23, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28542805/downregulation-of-cholesteryl-ester-transfer-protein-by-glucocorticoids-a-randomized-study-on-hdl
#17
Jorien Werumeus Buning, Lidya G Dimova, Frank G Perton, Uwe J F Tietge, André P van Beek, Robin P F Dullaart
BACKGROUND: High density lipoprotein (HDL) cholesterol is not decreased in hypercortisolism despite high triglycerides, which may be ascribed to effects on the cholesteryl ester transfer protein (CETP) pathway. We explored if CETP mRNA expression is modulated by glucocorticoid treatment in vitro. Effects of doubling the hydrocortisone (HCT) replacement dose on plasma CETP activity and HDL characteristics were tested in patients with secondary adrenal insufficiency. MATERIALS AND METHODS: Human THP-1 macrophages were incubated with corticosterone in vitro in the presence or absence of a liver X receptor (LXR) agonist, followed by determination of CETP mRNA levels by quantitative real-time PCR...
May 24, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28539336/nutritional-regulation-of-renal-lipogenic-factor-expression-in-mice-comparison-to-regulation-in-the-liver-and-skeletal-muscle
#18
Suk-Jeong Kim, Ji-Eun Kim, Yong-Woon Kim, Jong-Yeon Kim, So-Young Park
Regulation of lipogenesis by pathophysiological factors in the liver and skeletal muscle is well understood; however, regulation in the kidney is still unclear. To elucidate nutritional regulation of lipogenic factors in the kidney, we measured the renal expression of lipogenic transcriptional factors and enzymes during fasting and refeeding in chow-fed and high-fat-fed mice. We also examined the regulatory effect of the liver X receptor (LXR) on the expression of lipogenic factors. The renal gene expression of sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS) was reduced by fasting for 48 h and restored by refeeding, whereas the mRNA levels of forkhead box O (FOXO)1/3 were increased by fasting and restored by refeeding...
May 24, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28539318/serum-estradiol-levels-in-controlled-ovarian-stimulation-directly-affect-the-endometrium
#19
Kamran Ullah, Tanzil Ur Rahman, Hai-Tao Pan, Meng-Xi Guo, Xin-Yan Dong, Juan Liu, Lu-Yang Jin, Yi Cheng, Zhang-Hong Ke, Jun Ren, Xian-Hua Lin, Xiao-Xiao Qiu, Ting-Ting Wang, He-Feng Huang, Jian-Zhong Sheng
Previous studies have shown that increasing concentrations of estradiol had a toxic effect on the embryo and were deleterious to embryo adhesion. In this study, we evaluated the physiological impact of estradiol levels on endometrial cells to unveil that serum estradiol levels probably targeted endometrium in controlled ovarian hyperstimulation (COH) protocols. An attachment model of human choriocarcinoma (JAr) cell spheroids to receptive-phase endometrial epithelial cells and Ishikawa cells treated with different estradiol (10-9M or 10-7M) levels was developed...
May 24, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28536535/role-of-intestinal-lxr%C3%AE-in-regulating-post-prandial-lipid-excursion-and-diet-induced-hypercholesterolemia-and-hepatic-lipid-accumulation
#20
Tibiábin Benítez-Santana, Sarah E Hugo, Amnon Schlegel
Post-prandial hyperlipidemia has emerged as a cardiovascular risk factor with limited therapeutic options. The Liver X receptors (Lxrs) are nuclear hormone receptors that regulate cholesterol elimination. Knowledge of their role in regulating the absorption and handling of dietary fats is incomplete. The purpose of this study was to determine the role of intestinal Lxrα in post-prandial intestinal lipid transport. Using Lxrα knockout (nr1h3(-/-)) and intestine-limited Lxrα over-expressing [Tg(fabp2a:EGFP-nr1h3)] zebrafish strains, we measured post-prandial lipid excursion with live imaging in larvae and physiological methods in adults...
2017: Frontiers in Physiology
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